Human Marker Genes and Agents for Diagnosis, Treatment and Prophylaxis of Cardiovascular Disorders and Artherosclerosis

ABSTRACT

The invention relates to novel targets in the screening for compounds useful in the treatment and/or prophylaxis of a disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis. The invention relates to novel compounds for use as a medicament for diseases or conditions involving a disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis. The invention especially relates to antagonists and expression-inhibitory compounds that target G-protein coupled receptors (GPCRs), kinases and proteases, and to methods for identifying such compounds. The invention further relates to methods for identifying these antagonists and expression-inhibitory compounds, and methods for diagnosing a disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis or a susceptibility to such a condition.

FIELD OF THE INVENTION

The invention relates to novel targets for the screening of compounds useful in the treatment and prophylaxis or prevention of cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis. The invention also relates to novel compounds for use as a medicament for diseases or conditions involving Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis. The invention furthermore relates to antagonists and expression-inhibitory compounds that target G-protein coupled receptors (GPCRs), kinases and proteases of the invention, and to methods for identifying such compounds. The invention further relates to methods for identifying these antagonists and expression-inhibitory compounds, and methods for diagnosing Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis or a susceptibility to such a condition.

BACKGROUND OF THE INVENTION

Atherosclerosis is by far the single most important pathological process in the development of coronary heart disease (CHD), which is the single most common cause of morbidity and mortality in both men and women in developed nations. Atherosclerosis is a complex disease with multiple risk factors. It has been reported that 80-90% of patients who develop significant CHD and >95% of patients who experience fatal CHD have major atherosclerotic risk factors.

With regard to present day treatment of dyslipidemia, numerous well-controlled outcome studies of lipid-altering drug mono-therapy in >50000 subjects have consistently demonstrated a relative risk reduction (compared to placebo) of only 20-40% after 3-6 years of therapy. Hypercholesterolemia, or raised blood cholesterol levels, is the most prevalent cardiovascular condition, with a total prevalent condition of 320 million patients in the 8 major pharmaceutical markets. Standard therapy for atherosclerosis include lipid-lowering drugs: HMG-CoA reductase inhibitors (statins), PPAR-alpha agonists (fibrates) and niacin. Statins are the most recently launched class of anti-hypercholesterolemics and now dominate the hypercholesterolemic market. The majority of patients observed in mono-therapy trials of lipid-altering drugs have not had their CHD prevented. This suggests that further absolute and relative CHD risk will only be achieved through extending the duration of lipid-altering therapy, achieving more aggressive lipid treatment goals or treating multiple lipid parameters. It may also be reasonable to conclude that the best way to further reduce CHD risk is to aggressively correct the abnormality or abnormalities which contribute most to the atherosclerotic process in the individual patient. This may occur through mono-therapy, or through a multifactorial approach with the use of compounds addressing multiple risk factors. The US National Cholesterol Education Program (NCEP) has issued new guidelines that could significantly enhance the number of patients prescribed hypolipidemics in the US. The NCEP continues to identify LDL cholesterol as the primary target of therapy. Acceptable levels of LDL cholesterol as well as HDL cholesterol and triglycerides are more stringent than those in earlier guidelines. Therefore, additional lipid lowering therapies are needed (e.g., currently, half of patients treated with statins do not reach the new target LDL level).

Taken together, the therapeutic strategies currently available for treating Atherosclerosis are not satisfactory. As a major drawback, their limited efficacy calls for additional strategies to identify new medicaments with improved efficacy against Atherosclerosis.

Current approaches to lowering low density lipoprotein (LDL) cholesterol and therefore preventing the progression of Atherosclerosis include Squalene Synthase Inhibitors, intestinal bile acid transport (IBAT) protein inhibitors and SREBP cleavage-activating protein (SCAP) activating ligands. Other current approaches that affect lipid metabolism are microsomal triglyceride transfer protein (MTP) inhibitors, acylcoenzyme A: cholesterol acyltransferase (ACAT) inhibitors and nicotinic acid receptor (HM 74) agonists. Molecular targets involved in high density lipoprotein (HDL) cholesterol metabolism include cholesteryl ester transfer protein (CETP) with effective inhibitors under development, ATP-binding cassette transporter (ABC) A1 as well as scavenger receptor class B Type 1 (SRB1). Nuclear receptors as PPARs, LXR and FXR are also targets of investigational agents.

Because of the small number of available targets and because of the limited success in screening methods using available targets, a great need is felt in the art for promising targets and novel screening methods for compounds highly active in the treatment or Atherosclerosis.

The underlying technical problem of the present invention, therefore, can be seen as being the provision of novel screening methods, compounds, and molecular targets for the identification of compounds useful in the treatment and/or prophylaxis or prevention of Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis.

This problem is solved by the subject matter of the independent and dependent claims of the present patent application.

SUMMARY OF THE INVENTION

The invention relates to methods of screening compound libraries for compounds useful in the treatment and/or prophylaxis or prevention of Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis. The invention further relates to the molecular targets for use in said screening methods. Furthermore, the invention relates to kits and agents for use in screening methods of the invention, and to compounds found to bind to, or modulate, the molecular targets of the invention. In one aspect of the invention, it relates to methods of treatment of a subject in need, by administering agents that bind to, or modulate, targets of the invention. In another aspect of the invention, the invention relates to compounds that are identified using the methods according to the invention. The invention also relates to the use of any one of the target genes listed in Table 10, or of any one of the polypeptides encoded thereby, for the identification of compounds useful in the treatment and/or prophylaxis of Atherosclerosis. The invention furthermore relates to the use of a compound that decreases the activity and/or the expression of a polypeptide encoded by any one of the target genes listed in Table 10 in the manufacture of a medicament for the treatment and/or prophylaxis of Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis or a disease associated with Atherosclerosis. The invention furthermore relates to a method of reducing Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis in a subject, said method comprising the step of administering to a subject in need a pharmaceutical composition according to the invention.

BRIEF DESCRIPTION OF THE TABLES Table 1-12

The target list comprises screening data and gene specific information for 1277 siRNAs targeting 528 different genes, selected as positives from the total number of screened genes (target genes).

The selected genes were found positive by at least one of the three siRNAs tested per gene. As selection criteria, positive siRNAs showed an LDL-DiI uptake value of more than 2 standard deviations above the overall screen average value, corresponding to at least 314% of the unspecific control mean LDL-DiI uptake value measured in each screening plate of the primary screen.

The target list consists of 12 tables:

Table 1 contains numerical first pass screening values for LDL-DiI uptake (column 3, “LDL-DiI mean %”) and cell density (column 4, “proliferation mean %”, values normalized to the unspecific control siRNA) as well as the gene symbol (column 6, “target symbol”) and a functional classification (column 5, “Tar get Class(es)”) of the target genes.

Table 2 contains complementary information on the target genes consisting of the gene symbol (“column3, “target symbol”), RefSeq number (column 4, “RefSeq accession”), Entrez Gene ID (column 5) and a functional description derived from NCBI (column 6, “Target description”).

Table 3 indicates the nucleotide sequence of the sense strand of positive siRNAs (column 3, “siRNA sequence (21-mer)”).

Table 4 indicates the average expression level of the target genes in 3 different cell types: HepG2 human hepatoma cell line (column 4), HuH human hepatoma cell line (column 6) and human primary hepatoma cells (column 8).

Table 5 contains numerical screening values from secondary screening for Transferrin uptake (column 5, “Transferrin Run1 Mean %”; column 7, “Transferrin Run2 Mean %”; values normalized to the unspecific control siRNA) and the corresponding standard deviation (column 6, “Transferrin Run1 SD %”, column 8, “Transferrin Run2 SD %”). Included is as well as the target number (column 1, “Target No”), gene symbol (column 2, “target symbol”), the Entrez Gene ID (column 3, “Gene ID”) and the corresponding siRNA identificator (column 4, “siRNA ID”) of the target genes.

Table 6 contains numerical screening values from third pass screening for LDL-DiI uptake (column 6, “LDL-DiI Run1 Mean %”; column 8, “LDL-DiI Run2 Mean %”, column 10, “LDL-DiI Run3 Mean %”; values normalized to the unspecific control siRNA) and the corresponding standard deviation (column 7, “LDL-DiI Run1 SD %”, column 9, “LDL-DiI Run2 SD %”, column 11, “LDL-DiI Run2 SD %”). Column 5 indicates the applied siRNA concentration for each siRNA Oligo (100 nM “100”, 30 nM “30”, and 10 nM “10”). Included is as well as the target number (column 1, “Target No”), gene symbol (column 2, “target symbol”), the Entrez Gene ID (column 3, “Gene ID”) and the corresponding siRNA identificator (column 4, “siRNA ID”) of the target genes.

Table 7 contains numerical screening values from third pass screening for cell density (column 6, “Proliferation Run1 Mean %”; column 8, “Proliferation Run2 Mean %”; column 10, “Proliferation Run3 Mean %”; values normalized to the unspecific control siRNA) and the corresponding standard deviation (column 7, “Proliferation Run1 SD %”, column 9, “Proliferation Run2 SD %”, column 11, “Proliferation Run3 SD %”). Column 5 indicates the applied siRNA concentration for each siRNA Oligo (100 nM “100”, 30 nM “30”, and 10 nM “10”). Included is as well as the target number (column 1, “Target No”), gene symbol (column 2, “target symbol”), the Entrez Gene ID (column 3, “Gene ID”) and the corresponding siRNA identificator (column 4, “siRNA ID”) of the target genes.

Table 8 contains numerical values from third pass screening for remaining target mRNA expressed (column 6, “% mRNA Mean”; values normalized to the unspecific control siRNA). Column 5 indicates the applied siRNA concentration for each siRNA Oligo (100 nM “100”, 30 nM “30”, and 10 nM “10”). Included is as well as the target number (column 1, “Target No”), gene symbol (column 2, “target symbol”), the Entrez Gene ID (column 3, “Gene ID”) and the corresponding siRNA identificator (column 4, “siRNA ID”) of the target genes.

Table 9 indicates the nucleotide sequence of the sense strand of those siRNAs (column 3, “siRNA sequence (21-mer)”) used for the generation of the data presented in table 5 to table 12 and indicates the corresponding SEQ ID NO of each siRNA sequence.

Table 10 contains complementary information on specifically interesting genes. consisting of the gene symbol (“column2, “target symbol”), the Entrez Gene ID (column 3, “Gene ID”), RefSeq number (column 4, “RefSeq accession”) and a functional description derived from NCBI (column 5, “Target description”).

Table 11 contains numerical screening values from secondary screening for LDL-DiI uptake (column 5, “LDL-DiI Run1 Mean %”; column 7, “LDL-DiI Run2 Mean %”, values normalized to the unspecific control siRNA) and the corresponding standard deviation (column 6, “LDL-DiI Run1 SD %”, column 8, “LDL-DiI Run2 SD %”). Included is as well as the target number (column 1, “Target No”), gene symbol (column 2, “target symbol”), the Entrez Gene ID (column 3, “Gene ID”) and the corresponding siRNA identificator (column 4, “siRNA ID”) of the target genes.

Table 12 contains numerical screening values from secondary screening for cell density (column 5, “Proliferation Run1 Mean %”; column 7, “Proliferation Run2 Mean %”; values normalized to the unspecific control siRNA) and the corresponding standard deviation (column 6, “Proliferation Run1 SD %”, column 8, “Proliferation Run2 SD %”). Included is as well as the target number (column 1, “Target No”), gene symbol (column 2, “target symbol”), the Entrez Gene ID (column 3, “Gene ID”) and the corresponding siRNA identificator (column 4, “siRNA ID”) of the target genes.

The first column (“Target No”) of all tables assigns serial numbers to all target genes. siRNAs directed against the same gene have the same serial gene number.

DETAILED DESCRIPTION OF THE INVENTION

A human druggable genome siRNA library was screened in a cellular assay using Huh7 hepatoma cells. Read-out was expression of LDL-R as measured by binding of LDL-DiI. Targets whose downregulation resulted in an upregulation of LDL-R expression were scored as hits (see examples).

A “functional variant” of a first polynucleotide or polypeptide, within the meaning of the invention, shall be understood as being a second polynucleotide or polypeptide of preferably high sequence identity to said first polynucleotide or polypeptide, but being different in length and sequence, due to the addition and/or deletion and/or substitution of nucleotides or amino acid residues from said first polynucleotide or polypeptide, said second polynucleotide or polypeptide still having essentially the same characteristic biological activity as has the first polynucleotide or polypeptide. Such characteristic biological activity can be catalytic activity, binding properties, or other biological activities of the original molecule.

“Reference level”, within the meaning of the invention, shall be understood as being any reference level with which a measured level of, e.g., expression or activity can be compared to. Such reference levels can be obtained, e.g., from previous experiments or from literature.

“Wild-type level”, with respect to an expression level of a gene, shall be understood as being an expression level typically observed in wild-type organisms, i.e. in not recombinantly modified organisms of the same species.

“Binding affinity” of a molecule A to a protein P, within the meaning of the invention shall be understood as being the thermodynamic quantity that corresponds to the dissociation constant of the complex consisting of the molecule A and the protein P in a reaction A+P−−>AP under standard conditions. In this case the binding affinity is [A]*[B]/[AB], wherein square brackets symbolize the concentration of the respective species.

A “reporter gene” for a target protein, within the meaning of the invention, shall be understood as being a gene which is under control of a promotor which is influenced, directly or indirectly, by said target protein. Well known reporter genes are genes coding for fluorescent proteins under the control of a second messenger-dependent promotor.

“Nucleic acids”, within the meaning of the invention, shall be understood as being all known nucleic acids such as DNA, RNA, peptide nucleic acids, morpholinos, and nucleic acids with backbone structures other than phosphodiesters, such as phosphothiates or phosphoramidates.

The term “to comprise”, within the meaning of the invention, refers to nucleic acids in which the nucleic acids with the described sequences are functionally relevant, e.g. for diagnostic use or therapeutic use, such as vectors for therapeutic use or expression of corresponding proteins.

Preferably, any additional nucleic acids upstream or downstream of the sequence are not longer than 20 kb. The term “comprise” does not relate to large constructs accidentally including the sequence, such as genomic BAC or YAC clones.

“% identity” of a first sequence towards a second sequence, within the meaning of the invention, means the % identity which is calculated as follows: First the optimal global alignment between the two sequences is determined with the CLUSTALW algorithm [Thomson J D, Higgins D G, Gibson T J. 1994. ClustalW: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positions-specific gap penalties and weight matrix choice. Nucleic Acids Res., 22: 4673-4680], Version 1.8, applying the following command line syntax: ./clustalw-infile=./infile.txt -output=-outorder=aligned -pwmatrix=gonnet -pwdnamatrix=clustalw -pwgapopen=10.0 -pwgapext=0.1 -matrix=gonnet -gapopen=10.0 -gapext=0.05 -gapdist=8-hgapresidues=GPSNDQERK -maxdiv=40. Implementations of the CLUSTAL W algorithm are readily available at numerous sites on the internet, including, e.g., http://www.ebi.ac.uk. Thereafter, the number of matches in the alignment is determined by counting the number of identical nucleotides (or amino acid residues) in aligned positions. Finally, the total number of matches is divided by the number of nucleotides (or amino acid residues) of the longer of the two sequences, and multiplied by 100 to yield the % identity of the first sequence towards the second sequence.

“Arteriosclerosis”, within the meaning of the invention, is the thickening and hardening of the arteries due to the build-up of calcium deposits on the insides of the artery walls. Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis is a similar condition due to the build-up of fatty substances. Both conditions have similar effects on the circulation of the blood throughout the body. Heart disease, high blood pressure, stroke, and ischemia (starvation of the cells due to insufficient circulation) may be the result of arteriosclerosis and cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis. Within the context of this invention, “Atherosclerosis” shall be understood as encompassing both, Atherosclerosis and Arteriosclerosis as defined above.

The “nucleic acid expression vector” may be an extra-chromosomal entity, the replication of which is independent of chromosomal replication, e.g. a plasmid. Alternatively, the vector may be one which, when introduced into a host cell, particularly into a mammalian host cell, is integrated into the host cell genome and replicated together with the chromosome(s) into which it has been integrated. Preferably, the “nucleic acid expression vector” may be an expression vector which is usually applied in gene therapeutic methods in humans, particularly a retroviral vector or an adenoviral vector.

The term “expression cassette” is defined herein to include all components which are necessary or advantageous for the expression of a specific target polypeptide. An “expression cassette” may include, but is not limited to, the nucleic acid sequence of interest itself (e.g. encoding or corresponding to the siRNA or polypeptide of interest) and “control sequences”. These “control sequences” may include, but are not limited to, a promoter that is operatively linked to the nucleic acid sequence of interest, a ribosome binding site, translation initiation and termination signals and, optionally, a repressor gene or various activator genes. Control sequences are referred to as “homologous”, if they are naturally linked to the nucleic acid sequence of interest and referred to as “heterologous” if this is not the case. The term “operably linked” indicates that the sequences are arranged so that they function in concert for their intended purpose, i.e. expression of the desired protein, or, in case of RNA, transcription of the desired RNA.

The term “antibody” as used herein includes both polyclonal and monoclonal antibodies, as well as fragments thereof, such as Fv, Fab and F(ab)₂ fragments that are capable of binding antigen or hapten. The present invention also contemplates “humanized” hybrid antibodies wherein amino acid sequences of a non-human donor antibody exhibiting a desired antigen-specificity are combined with sequences of a human acceptor antibody. The donor sequences will usually include at least the antigen-binding amino acid residues of the donor but may comprise other structurally and/or functionally relevant amino acid residues of the donor antibody as well. Such hybrids can be prepared by several methods well known in the art.

The invention relates to 1. Method for identifying a compound as being useful in the treatment or prophylaxis of a disease, comprising the steps of

-   -   (a) providing a first cell expressing a target polypeptide         selected from the group listed in Table 10, or a fragment, or a         derivative thereof;     -   (b) exposing said first cell to a candidate compound;     -   (c) determining a first level of an activity or property, said         activity or property being affected by an activity or property         of said target polypeptide; and     -   (d) selecting or discarding said candidate compound, based on a         comparison of said first level of said activity or property with         a reference level of said activity or property;     -   characterised in that     -   said disease is a disease selected from the group comprising         cardiovascular diseases, disorders of lipid metabolism or         atherosclerosis.         2. Use of a method of Count 1 for the screening for substances         useful in the treatment or prophylaxis of A disease selected         from the group comprising cardiovascular diseases, disorders of         lipid metabolism or atherosclerosis.         3. Method of Count 1 or use of Count 2, wherein said host cell         expresses said target polypeptide above wild-type level.         4. Method or use of any of Counts 1 to 3, wherein said target         polypeptide expression is recombinant polypeptide expression.         5. Method or use of any of Counts 1 to 4, wherein said compound         is selected if said first level of said activity or property is         lower than said reference level of said activity or property.         6. Method or use of any of Counts 1 to 4, wherein said compound         is selected if said first level of said activity or property is         higher than said reference level of said activity or property.         7. Method or use of any of Counts 1 to 6, wherein said reference         level is a level obtained from a second cell expressing the         target polypeptide at a lower level as compared to said first         cell.         8. Method or use of any of Counts 1 to 6, wherein said reference         level is the level obtained with said first cell in the absence         of the candidate compound.         9. Method or use of any of Counts 1 to 8, wherein said method         further comprises contacting the host cell with a known agonist         or antagonist of the target polypeptide before determining the         first level.         10. Method or use of any of Counts 1 to 9, wherein said activity         or property being affected by said activity or property of said         target polypeptide is binding affinity of said compound to said         target polypeptide.         11. Use of a method, said method comprising the steps of     -   (a) culturing a population of cells expressing a target         polypeptide listed in Table 10, or a functional fragment or         derivative thereof;     -   (b) determining a first level of expression and/or activity of         said target protein in said population of cells;     -   (c) exposing said population of cells to a compound, or a         mixture of compounds;     -   (d) determining a second level of expression and/or activity of         said target polypeptide in said population of cells during or         after said exposure of said population of cells to the compound,         or the mixture of compounds; and     -   (e) comparing said first and said second level;         for the screening for substances useful in the treatment or         prophylaxis of A disease selected from the group comprising         cardiovascular diseases, disorders of lipid metabolism or         atherosclerosis.         12. Method or use of any of Counts 1 to 11, wherein said first         level of an activity or property is determined with a reporter,         said reporter being controlled by a promoter responsive to at         least one second messenger.         13. Method or use of Count 12, wherein said at least one second         messenger is cyclic AMP, or Ca2+, or both.         14. Method or use of Count 12 or 13, wherein said promoter is a         cyclic AMP-responsive promoter, an NF-KB responsive promoter, a         NF-AT responsive promoter, or a promoter responsive to         transcription factors or to nuclear hormone receptors.         15. Method or use of any of Counts 12 to 14, wherein the         reporter is luciferase or beta-galactosidase.         16. Method or use of any of Counts 1 to 15, wherein the compound         is a low molecular weight compound.         17. Method or use of any of Counts 1 to 15, wherein the compound         is a polypeptide.         18. Method or use of any of Counts 1 to 15, wherein the compound         is a lipid.         19. Method or use of any of Counts 1 to 15, wherein the compound         is a natural compound.         20. Method or use of any of Counts 1 to 15, wherein the compound         is an antibody or a nanobody.         21. Method for identifying a compound as being useful in the         treatment or prophylaxis of a disease, comprising the steps of     -   (a) contacting said compound with a target polypeptide selected         from the group listed in Table 10, or a fragment, or a         derivative thereof;     -   (b) detect binding of said compound to said target polypeptide         or detect a change in activity of said target polypeptide;     -   (c) selecting said compound If binding is detected in step (b)         or if a change in activity is detected in step (b);     -   characterised in that     -   said disease is A disease selected from the group comprising         cardiovascular diseases, disorders of lipid metabolism or         atherosclerosis.         22. Use of a method of count 21 for screening for compounds,         useful in the treatment or prophylaxis of A disease selected         from the group comprising cardiovascular diseases, disorders of         lipid metabolism or atherosclerosis.         23. Method or use of any of counts 21 to 22, wherein binding is         detected in vitro.         24. Method or use of any of counts 21 to 23, wherein said target         polypeptide is a recombinant polypeptide.

25. Method or use of any of counts 21 to 24, wherein said compound is selected if the binding affinity is equal to or lower than 10 micromolar.

26. Method or use of any of counts 21 to 25, wherein said compound is a low molecular weight compound. 27. Method or use of any of counts 21 to 25, wherein said compound is a polypeptide, or a lipid, or a natural compound, or an antibody or a nanobody. 28. Use of a compound that inhibits an activity and/or the expression of any of the polypeptides listed in Table 10 in the manufacture of a medicament for the treatment or prophylxis of A disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis. 29. Use of Count 28, wherein said compound is identified according to any one of the methods or uses of Counts 1 to 27. 30. Use of an agent inhibiting the expression of a polypeptide selected from the group listed in Table 10 for the preparation of a medicament for the treatment or prophylaxis of A disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis. 31. Use of Count 30, wherein said agent is selected from the group consisting of an antisense RNA encoding said polypeptide;

-   -   a ribozyme that cleaves the polyribonucleotide encoding said         polypeptide;     -   an antisense oligodeoxynucleotide (ODN) enconding said         polypeptide;     -   a small interfering RNA (siRNA) that is sufficiently homologous         to a portion of the polyribonucleotide such that said siRNA is         capable of inhibiting the polyribonucleotide that would         otherwise cause the production of said polypeptide;     -   a small interfering RNA (siRNA) having the sequence of any of         SEQ ID NO:1 to 172;     -   a microRNA (miRNA) suitable for inhibition of a polypeptide         selected from the group listed in Table 10; or     -   a short hairpin RNA (shRNA) suitable for silencing expression of         a polypeptide selected from the group listed in table 10.         32. Use of Count 31, wherein the nucleotide sequence of said         agent is present in a vector.         33. Use of Count 32, wherein the vector is an adenovirus, a         retrovirus, an alphavirus, an adeno-associated virus (AAV), a         lentivirus, a herpes simplex virus (HSV) or a sendai virus.         34. Use of any of Counts 31 to 33, wherein said agent is siRNA,         and said siRNA comprises a sense strand of 17 to 31 nucleotides         which is identical to a region of the coding sequence, or its         complementary sequence, of any of the polypeptides of Table 10.         35. Use of Count 34, wherein the siRNA further comprises a         cleavable loop region connecting the sense and the antisense         strand.         36. Vector comprising any of SEQ ID NO:1 to 172         37. Use of a vector of Count 36 as a medicament.         38. Use of a vector of Count 37 for the manufacture of a         medicament useful in the treatment or prophylaxis of A disease         selected from the group comprising cardiovascular diseases,         disorders of lipid metabolism or atherosclerosis.         39. Use according to Count 37 or 38, wherein the vector is an         adenoviral, retroviral, adeno-associated viral, lentiviral or a         sendaiviral vector.         40. Method for diagnosing a pathological condition involving A         disease selected from the group comprising cardiovascular         diseases, disorders of lipid metabolism or atherosclerosis, or a         susceptibility to said condition in a subject, comprising     -   (a) obtaining a sample of the subject's mRNA corresponding to a         polypeptide selected from the group listed in Table 10, or a         sample of the subject's genomic DNA corresponding to a         polypeptide of Table 10;     -   (b) determining the nucleic acid sequence of said mRNA or said         genomic DNA;     -   (c) obtaining the nucleic acid sequence encoding said         polypeptide of Table 10 from a public database; and     -   (d) identifying any difference(s) between the nucleic acid         sequences determined in step (b) and (c);         wherein a pathological condition involving a disease selected         from the group comprising cardiovascular diseases, disorders of         lipid metabolism or a disease selected from the group comprising         cardiovascular diseases, disorders of lipid metabolism or         atherosclerosis, or a susceptibility to such a condition in a         subject is diagnosed, if such difference(s) are identified in         step (d).         41. Method for diagnosing a pathological condition involving A         disease selected from the group comprising cardiovascular         diseases, disorders of lipid metabolism or atherosclerosis or a         susceptibility to such a condition in a subject, comprising     -   (a) determining the amount of a polypeptide of Table 10 in a         biological sample of said subject; and     -   (b) comparing the amount determined in (a) with a the amount of         the polypeptide in a healthy subject;         wherein an increase or a decrease of the amount of said         polypeptide compared to the amount present in a healthy subject         is indicative of the presence of the pathological condition.

One further embodiment of the invention is the use of the genes/proteins listed in Table 10 as therapeutical targets in the field of cardiovascular diseases, preferably lipid metabolism disorders or atherosclerosis.

Furthermore, those targets listed in Table 10 are preferred, which are highly expressed in HepG2 cells, Huh cells, primary hepatocytes, and whole liver cells. Those targets of Table 10, which show an average expression of above 1000 in HepG2 cells, Huh cells, primary hepatocytes, or whole liver cells, in Table 4, are preferred targets of the invention. Even more preferred are targets of Table 10, which show an average expression of above 1000 in at least two, or three or (most preferred) four cell types, in a list of cell types consisting of HepG2 cells, Huh cells, primary hepatocytes, and whole liver cells, in Table 4.

Furthermore, those targets listed in Table 10 are preferred, which show an increase in LDL-DiI uptake with more than one siRNA oligo in the primary and/or secondary screening (Table 1 and Table 11) and show no significant alteration in cellular proliferation (Table 12). Furthermore, those targets listed in Table 10 are preferred, which show increased LDL-DiI uptake (Table 11) without any similarly strong increase in Transferrin uptake (Table 5). Furthermore, those targets listed in Table 10 are preferred, which show a strongly increased LDL-DiI uptake (Table 11) with at least one siRNA oligo.

According to a further preferred embodiment, the nucleic acid molecules may also have the antisense-sequence of any of the sequences of the invention. According to a further embodiment, fragments or functional variants of the nucleic acid molecules as described above may be used. According to a further embodiment, the nucleic acid molecule comprises a nucleotide sequence which is capable of hybridizing with the nucleic acid sequences of the invention under conditions of medium/high stringency. In such hybrids, duplex formation and stability depend on substantial complementarity between the two strands of the hybrid and a certain degree of mismatch can be tolerated. Therefore, the nucleic acid molecules and probes of the present invention may include mutations (both single and multiple), deletions, insertions of the above identified sequences, and combinations thereof, as long as said sequence variants still have substantial sequence similarity to the original sequence which permits the formation of stable hybrids with the target nucleotide sequence of interest. Suitable experimental conditions for determining whether a given DNA or RNA sequence “hybridizes” to a specified polynucleotide or oligonucleotide probe involve pre-soaking of the filter containing the DNA or RNA to examine for hybridization in 5×SSC (sodium chloride/sodium citrate) buffer for 10 minutes, and pre-hybridization of the filter in a solution of 5×SSC, 5×Denhardt's solution, 0.5% SDS and 100 mg/ml of denaturated sonicated salmon sperm DNA (Maniatis et al., 1989), followed by hybridization in the same solution containing a concentration of 10 ng/ml of a random primed (Feinberg, A. P. and Vogelstein, B. (1983), Anal. Biochem. 132:6-13), ³²P-dCTP-labeled (specific activity >1×10⁹ cpm/μg) probe for 12 hours at approximately 45° C. The filter is then washed twice for 30 minutes in 2×SSC, 0.5% SDS at least 55° C. (low stringency), at least 60° C. (medium stringency), preferably at least 65° C. (medium/high stringency), more preferably at least 70° C. (high stringency) or most preferably at least 75° C. (very high stringency). Molecules to which the probe hybridizes under the chosen conditions are detected using an x-ray film or a “phosphor imager”. “Suitable conditions” for the production of the above double-stranded RNA-molecule are all in vivo or in vitro conditions that according to the state of art allow the expression of a first and a second RNA-strand with the above sequences and lengths that—when hybridized—form a double-stranded RNA-molecule. Particularly preferred “suitable conditions” for the production of the above double-stranded RNA-molecule are the “in vivo conditions” in a living human or animal cell or the “in vitro conditions” in cultured human or animal cells.

The isolated nucleic acid molecules of the invention, or their modulators/regulators may be used for treating or diagnosing Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis either in vitro or in vivo.

Treatment and/or prophylaxis of Artherosclerosis using said nucleic acid molecules can be achieved in different ways familiar to the person skilled in the art. For example, the isolated nucleic acid molecules may be inserted downstream of a strong promotor to overexpress the corresponding protein or polypeptide. Overexpression of the protein or polypeptide may lead to suppression of the endogenous protein's biological function. By introducing deletions or other mutations into the nucleic acids, or by using suitable fragments, it is possible to generate sequences encoding dominant-negative peptides or polypeptides. Such dominant-negative peptides or polypeptides can inhibit the function of the corresponding endogenous protein.

According to a further preferred embodiment, the invention relates to the use of the above identified nucleic acid molecules or functional variants thereof in form of RNA, particularly antisense RNA and double-stranded RNA, for the manufacture of a medicament for the treatment and/or prophylaxis of Artherosclerosis. Also ribozymes can be generated for the above identified sequences and used to degrade RNA transcribed from the corresponding endogenous genes.

Particularly preferred is the use of these RNA molecules in a therapeutic application of the RNAi technique, particularly in humans or in human cells. An RNAi technique particularly suited for mammalian cells makes use of double-stranded RNA oligonucleotides known as “small interfering RNA” (siRNA).

Therefore, according to a further preferred embodiment, the invention relates to the use of nucleic molecules comprising small interfering RNA with a sequence corresponding to any of the sequences given in table 3.

These siRNA molecules can be used for the therapeutic silencing of the expression of the genes of the invention comprising nucleic acid sequences of the invention, in mammalian cells, particularly in human cells, particularly for the therapy of Artherosclerosis.

The inhibition of a specific target gene in mammals is achieved by the introduction of an siRNA-molecule having a sequence that is specific (see above) for the target gene into the mammalian cell. The siRNAs comprise a first and a second RNA strand, both hybridized to each other, wherein the sequence of the first RNA strand is a fragment of one of the sequences of the invention and wherein the sequence of the second RNA strand is the antisense-strand of the first RNA strand. The siRNA-molecules may possess a characteristic 2- or 3-nucleotide 3′-overhanging sequence. Each strand of the siRNA molecule preferably has a length of 19 to 31 nucleotides.

The siRNAs can be introduced into the mammalian cell by any suitable known method of cell transfection, particularly lipofection, electroporation or microinjection. The RNA oligonucleotides can be generated and hybridized to each other in vitro or in vivo according to any of the known RNA synthesis methods.

In another embodiment, the invention relates to the use of a nucleic acid molecule as defined above, wherein the nucleic acid molecule is contained in at least one nucleic acid expression vector which is capable of producing a double-stranded RNA-molecule comprising a sense-RNA-stand and an antisense-RNA-strand under suitable conditions, wherein each RNA-strand, independently from the other, has a length of 19 to 31 nucleotides.

In this alternative method (also described in Tuschl, Nature Biotechnology, Vol. 20, pp. 446-448), vector systems capable of producing siRNAs instead of the siRNAs themselves are introduced into the mammalian cell for down-regulating gene expression. The preferred lengths of the RNA-strands produced by such vectors correspond to those preferred for siRNAs in general (see below).

microRNAs (miRNAs) are evolutionarily conserved small non-protein-coding RNA gene products that regulate gene expression at the post-transcriptional level. In animals, mature miRNAs are ˜22 nucleotides long and are generated from a primary transcript through sequential processing by nucleases belonging to the RNAseIII family.

An alternative to transfecting cells with chemically synthesized siRNAs are DNA-vector-mediated mechanisms to express substrates that can be converted into siRNA in vivo. In the first approach the sense and antisense strands of the siRNA are expressed from different, usually tandem promoters. Alternatively, short hairpin (sh)RNAs are expressed and processed by Dicer into siRNAs. In general, chemically synthesized short interfering (si)RNA sequences that are effective at silencing gene expression are also effective when generated from short hairpin (sh)RNAs. However, the length of the stem and the size and composition of the loop are important for the efficiency of silencing.

The coding sequence of interest may, if necessary, be operably linked to a suitable terminator or to a poly-adenylation sequence. In the case of RNA, particularly siRNA, “coding sequence” refers to the sequence encoding or corresponding to the relevant RNA strand or RNA strands.

Further, the vector may comprise a DNA sequence enabling the vector to replicate in the mammalian host cell. Examples of such a sequence—particularly when the host cell is a mammalian cell—is the SV40 origin of replication.

A number of vectors suitable for expression in mammalian cells are known in the art and several of them are commercially available. Some commercially available mammalian expression vectors which may be suitable include, but are not limited to, pMC1neo (Stratagene), pXT1 (Stratagene), pSG5 (Stratagene), pcDNAI (Invitrogen), EBO-pSV2-neo (ATCC 37593), pBPV-1(8-2) (ATCC 37110), pSV2-dhfr (ATCC 37146). Preferred are all suitable gene therapeutic vectors known in the art.

In a particularly preferred embodiment of the invention the vector is a retroviral vector. Retroviruses are RNA-viruses possessing a genome that after the infection of a cell, such as a human cell, is reversely transcribed in DNA and subsequently is integrated into the genome of the host cell. Retroviruses enter their host cell by receptor-mediated endocytosis. After the endocytosis into the cell the expression of the retroviral vector may be silenced to ensure that only a single cell is infected. The integration of the viral DNA into the genome is mediated by a virus-encoded protein called integrase, wherein the integration locus is not defined. Retroviral vectors are particularly appropriate for their use in gene therapeutic methods, since their transfer by receptor-mediated endocytosis into the host cell, also known to those skilled in the art as “retroviral transduction” is particularly efficient. A person skilled in the art also knows how to introduce such retroviral vectors into the host cell using so called “packaging cells”.

In another particularly preferred embodiment of the invention, the vector is an adenoviral vector or a derivative thereof. Adenoviral vectors comprise both replication-capable and replication-deficient vectors. The latter include vectors deficient in the E1 gene.

The recombinant vector is preferably introduced into the mammalian host cells by a suitable pharmaceutical carrier that allows transformation or transfection of the mammalian, in particular human cells. Preferred transformation/transfection techniques include, but are not limited to liposome-mediated transfection, virus-mediated transfection and calcium phosphate transfection.

In a preferred embodiment, the invention relates to the use of a vector system capable of producing siRNAs as defined above, wherein the nucleic acid corresponding to the siRNA is contained in at least one nucleic acid expression vector comprising a first expression cassette containing the nucleic acid corresponding to the sense-RNA-strand under the control of a first promoter and a second expression cassette containing the nucleic acid corresponding to the antisense-RNA-strand under the control of a second promoter.

In the above mentioned vector system, the vector comprises two individual promoters, wherein the first promoter controls the transcription of the sense-strand and the second promoter controls the transcription of the antisense strand (also described in Tuschl, Nature Biotechnology, Vol. 20, pp. 446-448). Finally the siRNA duplex is constituted by the hybridisation of the first and the second RNA-strand.

The promoter used in the aforementioned “expression cassettes” may be any DNA sequence which shows transcriptional activity in a host cell of choice, preferably in a mammalian host cell, particularly in a human host cell. The promoter may be derived from genes encoding proteins either homologous or heterologous to the host cell.

As a promoter in general every promoter known in the prior art can be used that allows the expression of the gene of interest under appropriate conditions in a mammalian host cell, in particular in a human host cell. Particularly promoters derived from RNA polymerase III transcription units, which normally encode the small nuclear RNAs (snRNAs) U6 or the human RNAse P RNA H1, can be used as promoters to express the therapeutic siRNAs. These particularly preferred promoters U6 and H1 RNA which are members of the type III class of Polymerase III promoters are—with the exception of the first transcribed nucleotide (+1 position)—only located upstream of the transcribed region.

In a preferred embodiment, the invention relates to the use of a vector system capable of producing siRNAs for the above identified nucleic acid sequences, wherein the sequence is contained in at least one nucleic acid expression vector comprising an expression cassette containing the sequence of the sense-RNA-strand and of the antisense-RNA-strand under the control of a promoter leading to a single-stranded RNA-molecule and wherein the single-stranded RNA-molecule is capable of forming a back-folded stem-loop-structure.

In this vector system (also described in Tuschl, Nature Biotechnology, Vol. 20, pp. 446-448), only a single RNA-strand is produced under the control of a single promoter, wherein the RNA strand comprises both the sense- and of the antisense-strand of the final double-stranded siRNA molecule. This structure leads to a back-folding of the RNA-strand by hybridisation of the complementary sense- and antisense-sequences under stem-loop formation. Finally the intracellular processing of this fold-back stem-loop-structure gives rise to siRNA.

In another preferred embodiment according to the present invention, the “nucleic acid expression vector” comprises an expression cassette containing the sequence of the sense-RNA-strand and of the antisense-RNA-strand both under the control of a single promoter leading to a single-stranded RNA-molecule. This single-stranded RNA-molecule is hereby capable to form a back-folded stem-loop-structure. These expressed “hairpin RNA-molecules” subsequently give rise to siRNAs after intracellular processing.

In a preferred embodiment of the invention the nucleic acid expression vector that gives rise to the expression of siRNAs according to the present invention is first introduced into therapeutic, non-toxic virus particles or virus-derived particles that are suitable for gene therapeutic applications and that can infect mammalian, in particular human target cells, such as packaging cells etc.

In a preferred embodiment, the first and the second RNA strand of the siRNA may have, independently from the other, a length of 19 to 25 nucleotides, more preferred of 20 to 25 nucleotides, and most preferred of 20 to 22 nucleotides.

In another preferred embodiment, the first and the second RNA strand of the siRNA may have, independently from the other, a length of 26 to 30 nucleotides, more preferred of 26 to 28 nucleotides, and most preferred of 27 nucleotides.

In another aspect, the invention relates to the use of isolated proteins or polypeptides comprising a sequence selected from the group consisting of

-   -   (a) a sequence as disclosed by the corresponding accession         number in table 10;     -   (b) a sequence that exhibits a sequence identity with any of the         sequences according to (a) of at least 90% over at least 100         residues,     -   (c) or functional variants of the sequences defined in (a) or         (b),         for the manufacture of a medicament for the treatment and/or         prophylaxis of Cardiovascular diseases, preferably disorders of         lipid metabolism and atherosclerosis.

Proteins, polypeptides and peptides can be introduced into the cells by various methods known in the art. For example, amphiphilic molecules may be membrane permeable and can enter cells directly. Membrane-bound proteins or polypeptides (usually lipophilic molecules or containing transmembrane domains) may insert directly into cell membranes and can thus exert their biological function. Other ways of introduction or intracellular uptake include microinjection, lipofection, receptor-mediated endocytosis, or the use of suitable carrier-molecules, particularly carrier-peptides. Suitable carrier-peptides include or can be derived from HIV-tat, antennapedia-related peptides (penetratins), galparan (transportan), polyarginine-containing peptides or polypeptides, Pep-1, herpes simplex virus VP-22 protein. Another possible introduction method is to introduce nucleic acid vectors capable of expressing such proteins, polypeptides or peptides.

Suitable methods to produce isolated polypeptides are known in the art. For example, such a method may comprise transferring the expression vector with an operably linked nucleic acid molecule encoding the polypeptide into a suitable host cell, cultivating said host cells under conditions which will permit the expression of said polypeptide or fragment thereof and, optionally, secretion of the expressed polypeptide into the culture medium. Depending on the cell-type different desired modifications, e.g. glycosylation, can be achieved.

The proteins, polypeptides and peptides may also be produced synthetically, e.g. by solid phase synthesis (Merrifield synthesis).

The polypeptides used in the invention may also include fusion polypeptides. In such fusion polypeptides another polypeptide may be fused at the N-terminus or the C-terminus of the polypeptide of interest or fragment thereof. A fusion polypeptide is produced by fusing a nucleic acid sequence (or a portion thereof) encoding another polypeptide to a nucleic acid sequence (or a portion thereof) of the present invention. Techniques for producing fusion polypeptides are known in the art and include ligating the coding sequences so that they are in frame and the expression of the fusion polypeptide is under control of the same promotor(s) and terminator.

Expression of the polypeptides of interest may also be performed using in vitro produced synthetic mRNA. Synthetic mRNA can be efficiently translated in various cell-free systems, including but not limited to, wheat germ extracts and reticulocyte extracts, as well as efficiently translated in cell based systems including, but not limited to, microinjection into frog oocytes, preferably Xenopus laevis oocytes.

Treatment and/or prophylaxis of Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis, using said isolated proteins or polypeptides, can be achieved by different ways familiar to the person skilled in the art: Overexpression of the protein or polypeptide may lead to suppression of the endogenous protein's biological function. By introducing deletions or other mutations, or by using suitable fragments, it is possible to generate sequences encoding dominant-negative peptides or polypeptides. Such dominant-negative peptides or polypeptides can inhibit the function of the corresponding endogenous protein. For example, functional variants or mutants can be generated which consist only of binding domains but are enzymatically inactive (i.e. partially lacking their biological function). Such dominant-negative molecules may interfere with the biological function of the endogenous proteins or polypeptides by binding to intracellular binding partners and thus blocking activation of the endogenous molecule.

In another aspect, the invention relates to the use of an antibody which is directed against at least one polypeptide comprising a sequence as defined above for the manufacture of a medicament for the treatment and/or prophylaxis of Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis.

The term “antibody” as used herein includes both polyclonal and monoclonal antibodies, as well as fragments thereof, such as Fv, Fab and F(ab)₂ fragments that are capable of binding antigen or hapten. The present invention also contemplates “humanized” hybrid antibodies wherein amino acid sequences of a non-human donor antibody exhibiting a desired antigen-specificity are combined with sequences of a human acceptor antibody. The donor sequences will usually include at least the antigen-binding amino acid residues of the donor but may comprise other structurally and/or functionally relevant amino acid residues of the donor antibody as well. Such hybrids can be prepared by several methods well known in the art.

Antibodies specifically binding to proteins of the invention, or suitable fragments thereof, particularly in humanized form, may be used as therapeutic agents in a method for treating Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis. The use of said antibodies may also include the therapeutical inhibition of the above identified nucleic acid molecules or their corresponding polypeptides. In particular, this use may be directed to

Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis. The antibodies or fragments may be introduced into the body by any method known in the art. Delivery of antibodies, particularly of fragments, into live cells may be performed as described for peptides, polypeptides and proteins. If the antigen is extracellular or an extracellular domain, the antibody may exert its function by binding to this domain, without need for intracellular delivery.

Antibodies can be coupled covalently to a detectable label, such as a radiolabel, enzyme label, luminescent label, fluorescent label or the like, using linker technology established for this purpose. Labeling is particularly useful for diagnostic purposes (see below) or for monitoring the distribution of the antibody within the body or a neoplastic tumor, e.g. by computed tomography, PET (positron emission tomography), or SPECT (single photon emission computed tomography).

In another aspect, the invention relates to the use of an isolated nucleic acid molecule comprising a nucleic acid with a sequence selected from the group of sequences consisting of:

-   -   a) the nucleic acid sequences presented by the corresponding         accession number in table 10;     -   b) nucleic acid sequences encoding polypeptides that exhibit a         sequence identity with the protein encoded by a nucleic acid         according to a) of at least 90% over at least 100 residues         and/or which are detectable in a computer aided search using the         BLAST sequence analysis programs with an e-value of at most         10⁻⁵,     -   c) sequences of nucleic acid molecules which are capable of         hybridizing with the nucleic acid molecules with sequences         corresponding to (a) or (b) under conditions of medium or high         stringency,     -   d) the antisense-sequence of any of the sequences as defined in         (a), (b) or (c),     -   e) functional variants of (a), (b), (c) or (d),     -   f) RNA sequences corresponding to any of the sequences as         defined in (a), (b), (c), (d), or (e),         for the manufacture of a medicament for the activation of         Cardiovascular diseases, preferably disorders of lipid         metabolism and atherosclerosis.

In another aspect, the invention relates to the use of a an isolated peptide or polypeptide comprising a peptide or polypeptide with a sequence selected from the group consisting of:

-   -   (a) a sequence as disclosed by the corresponding accession         number in table 10;     -   (b) a sequence that exhibits a sequence identity with any of the         sequences according to (a) of at least 90% over 100 residues.     -   (c) functional variants of the sequences defined in (a) or (b),         for the manufacture of a medicament for the treatment and/or         prophylaxis of Cardiovascular diseases, preferably disorders of         lipid metabolism and atherosclerosis.

In another aspect, the invention relates to the use of an antibody which is directed against at least one peptide or polypeptide with a sequence as defined above for the manufacture of a medicament for the treatment and/or prevention of cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis.

Expression of RNA or polypeptides may be achieved by introduction of genomic DNA or cDNA containing suitable promoters, preferably constitutive or homologous promoters. Alternatively, any suitable nucleic acid expression vector can be used. The encoded protein or polypeptide may be full-length or a fragment or peptide with a similar biological function.

The proteins, polypeptides or peptides may also be generated by any known in vivo or in vitro method and introduced directly into the cells.

It is known that suitable antibodies can be used to activate the biological function of target proteins they bind to. Activation may occur by inducing conformational changes upon binding to the target protein. Another possibility is that the antibody binds two or more target proteins and brings them into sufficiently close physical proximity to induce interaction of the target proteins. The latter mode of activation is particularly known for membrane-bound dimeric receptors.

With respect to the specific embodiments relating to the used nucleic acids, peptides, polypeptides, proteins, and antibodies the same applies as defined above for the other uses of the invention.

In another embodiment, the invention relates to a medicament containing an isolated nucleic acid molecule, peptide, polypeptide, or antibody selected from the group consisting of

-   -   a) nucleic acid molecules or nucleic acid expression vectors as         defined above,     -   b) a peptide or polypeptide comprising a sequence as defined         above,     -   c) an antibody directed against at least one peptide or         polypeptide according to (b).

Preferably this isolated nucleic acid molecule is an RNA molecule and preferably is double-stranded. Particularly the isolated nucleic acid molecule is an siRNA molecule according to the present invention.

The following considerations for medicaments and their administration apply also to the medicaments of the invention as to the above disclosed uses.

The medicament preferably comprises additionally a suitable pharmaceutically acceptable carrier, preferably virus-particles or virus-derived particles that may harbour the viral vectors, transfection solutions comprising liposomes, particularly cationic liposomes, calcium phosphate etc. Preferably a carrier is used, which is capable of increasing the efficacy of the expression vector or virus particles containing the expression vector to enter the mammalian target cells. The medicament may additionally comprise other carrier substances, preferably starch, lactose, fats, stearin acid, alcohol, physiological NaCl-solutions or further additives, in particular stabilizers, preservatives, dyes and flavourings.

The medicaments may also comprise other suitable substances. For example, RNA or siRNA containing medicaments may contain substances which stabilize double-stranded RNA molecule and/or which enable the double-stranded RNA molecule or DNA expression vector to be transfected or to be injected into the human or animal cell.

Administration can be carried out by known methods, wherein a nucleic acid is introduced into a desired cell in vitro or in vivo. For therapeutic applications, the medicament may be in form of a solution, in particular an injectable solution, a cream, ointment, tablet, suspension, granulate or the like. The medicament may be administered in any suitable way, in particular by injection, by oral, nasal, rectal application. The medicament may particularly be administered parenteral, that means without entering the digestion apparatus, for example by subcutaneous injection. The medicament may also be injected intravenously in the form of solutions for infusions or injections. Other suitable administration forms may be direct administrations on the skin in the form of creams, ointments, sprays and other transdermal therapeutic substances or in the form of inhalative substances, such as nose sprays, aerosoles or in the form of microcapsules or implantates.

The optimal administration form and/or administration dosis for a medicament either comprising double-stranded RNA molecules with the above sequences or comprising nucleic acid vectors capable to express such double-stranded RNA molecules depend on the type and the progression of the disease to be treated.

In another embodiment of the invention, an activator or an inhibitor of a protein of the invention can be administered to a patient in need.

Preferably, the activator or inhibitor is administered in pharmaceutically effective amount. As used herein, a “pharmaceutically effective amount” of an activator or inhibitor is an amount effective to achieve the desired physiological result, either in cells treated in vitro or in a subject treated in vivo. Specifically, a pharmaceutically effective amount is an amount sufficient to positively influence, for some period of time, one or more clinically defined pathological effects associated with Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis. The pharmaceutically effective amount may vary depending on the specific activator or inhibitor selected, and is also dependent on a variety of factors and conditions related to the subject to be treated and the severity of the disease. For example, if the activator or inhibitor is to be administered in vivo, factors such as age, weight, sex, and general health of the patient as well as dose response curves and toxicity data obtained in pre-clinical animal tests would be among the factors to be considered. If the activator or inhibitor is to be contacted with cells in vitro, one would also design a variety of pre-clinical in vitro studies to assess parameters like uptake, half-life, dose, toxicity etc. The determination of a pharmaceutically effective amount for a given agent (activator or inhibitor) is well within the ability of those skilled in the art. Preferably, the activator or inhibitor is present in a concentration of 0.1 to 50% per weight of the pharmaceutical composition, more preferably 10 to 30%.

An inhibitor, activator, or drug according to the present invention may also be a “small molecule”. Small molecules are molecules which are not proteins, peptides antibodies or nucleic acids, and which exhibit a molecular weight of less than 5000 Da, preferably less than 2000 Da, more preferably less than 2000 Da, most preferably less than 500 Da. Such small molecules may be identified in high throughput procedures/screening assays starting from libraries. Such methods are known in the art. Suitable small molecules can also be designed or further modified by methods known as combinatorial chemistry.

In another aspect, the present invention relates to the use of an isolated nucleic acid molecule comprising a sequence as defined above or the use of a ligand binding specifically at least one polypeptide comprising a sequence as defined above for the in vitro diagnosis of Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis.

The diagnostic use of the above identified nucleic acid molecules and probes may include, but is not limited to the quantitative detection of expression of said target genes in biological probes (preferably, but not limited to tissue samples, cell extracts, body fluids, etc.), particularly by quantitative hybridization to the endogenous nucleic acid molecules comprising the above-characterized nucleic acid sequences (particularly cDNA, RNA)

The invention further relates to methods for diagnosis a pathological condition involving Atherosclerosis in a subject, said methods comprising the steps of: (a) determining the nucleic acid sequence of one of the target genes listed in Table 10 within the genomic DNA of said subject; (b) comparing the sequence from step (a) with the nucleic acid sequence obtained from a database and/or a healthy subject; and identifying any difference(s) related to the onset of Atherosclerosis.

Expression of the endogenous genes or their corresponding proteins can be analyzed in vitro in tissue samples, body fluids, and tissue and cell extracts. Expression analysis can be performed by any method known in the art, such as RNA in situ hybridization, PCR (including quantitative RT-PCR), and various serological or immunological assays which include, but are not limited to, precipitation, passive agglutination, enzyme-linked immunosorbent antibody (ELISA) technique and radioimmunoassay techniques.

The diagnostic use may also include the detection of mutations in endogenous genes corresponding to the above identified nucleic acid sequences.

Suitable nucleic acid probes may be synthesized by use of DNA synthesizers according to standard procedures or, preferably for long sequences, by use of PCR technology with a selected template sequence and selected primers. The probes may be labeled with any suitable label known to those skilled in the art, including radioactive and non-radioactive labels. Typical radioactive labels include ³²P, ¹²⁵I, ³⁵S, or the like. A probe labeled with a radioactive isotope can be constructed from a DNA template by a conventional nick translation reaction using a DNase and DNA polymerase. Non-radioactive labels include, for example, ligands such as biotin or thyroxin, or various luminescent or fluorescent compounds. The probe may also be labeled at both ends with different types of labels, for example with an isotopic label at one end and a biotin label at the other end. The labeled probe and sample can then be combined in a hybridization buffer solution and held at an appropriate temperature until annealing occurs. Such nucleic acid probes may also be used for other than diagnostic purposes, e.g. for the identification of further homologs or orthologs.

“Ligands” binding specifically to said polypeptides are known in the art. Such ligands include proteins or polypeptides, for example intracellular binding partners, antibodies, molecular affinity bodies, and small molecules. Specifically binding ligands can be identified by standard screening assays known in the art (see also below), for example by yeast two-hybrid screens and affinity chromatography. A specifically binding ligand does not need to exert another function such as inhibiting or activating the molecule with which it interacts.

In a preferred embodiment, the ligand is an antibody binding specifically at least one polypeptide comprising a sequence as defined above.

“Specific binding” according to the present invention means that the polypeptide to be identified (the target polypeptide) is bound with higher affinity than any other polypeptides present in the sample. Preferred is at least 3 times higher affinity, more preferred at least 10 times higher affinity, and most preferred at least 50 times higher affinity. Non-specific binding (“cross-reactivity”) may be tolerable if the target polypeptide can be identified unequivocally, e.g. by its size on a Western blot.

Preferably the specifically binding ligands can be labeled, e.g. with fluorescent labels, enzymes, molecular tags (e.g. GST, myc-tag or the like), radioactive isotopes, or with labeled substances, e.g. labeled secondary antibodies. For MRI (magnetic resonance imaging), the ligands may be chelated with gadolinium, superparamagnetic iron oxide or lanthanides. For PET (positron emission tomography) or SPECT (single photon emission computed tomography) commonly used isotopes include ¹¹C, ¹⁸F, ¹⁵O, ¹³N, ⁸⁶Y, ⁹⁰Y, and ¹⁶Co.

Diagnostic kits may comprise suitable isolated nucleic acid or amino acid sequences of the above identified genes or gene products, labelled or unlabelled, and/or specifically binding ligands (e.g. antibodies) thereto and auxiliary reagents as appropriate and known in the art. The assays may be liquid phase assays as well as solid phase assays (i.e. with one or more reagents immobilized on a support). The diagnostic kits may also include ligands directed towards other molecules indicative of the disease to be diagnosed.

In another aspect, the invention relates to the use of an isolated nucleic acid molecule or a nucleic acid expression vectors as defined above or of an antibody which is directed against at least one polypeptide comprising a sequence as defined above, in a screening assay for the identification and characterization of drugs that are useful in the treatment and/or prophylaxis of Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis.

“Screening assay” according to the present invention relates to assays which allow to identify substances, particularly potential drugs, useful in the treatment and/or prophylaxis of Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis, by screening libraries of substances. “Screening assay” according to the present invention also relates to assays to screen libraries for substances capable of binding to the nucleic acids, polypeptides, peptides or antibodies defined above. Suitable libraries may, for example, include small molecules, peptides, polypeptides or antibodies.

Suitable drugs include “interacting drugs”, i.e. drugs that bind to the polypeptides or nucleic acids identified above. Such interacting drugs may either inhibit or activate the molecule they are bound to. Examples for interacting substances are peptide nucleic acids comprising sequences identified above, antisense RNAs, siRNAs, ribozymes, aptamers, antibodies and molecular affinity bodies (CatchMabs, Netherlands). Such drugs may be used according to any aspect of the present invention, including use for the manufacture of medicaments and methods of treatment and/or prophylaxis of Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis. It is known that such interacting drugs can also be labeled and used as ligands for diagnosis of a disease associated Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis.

The term “expression vector” as used herein does not only relate to RNA or siRNA expressing vectors, but also to vectors expressing peptides, polypeptides or proteins. The transfer of the expression vector into the host cell or host organism hereby may be performed by all known transformation or transfection techniques, including, but not limited to calcium phosphate transformation, lipofection, microinjection. The expression vector may be any known vector that is suitable to allow the expression of the nucleic acid sequence as defined above. Preferred expression vectors possess expression cassettes comprising a promoter that allows an overexpression of the RNA, peptide or polypeptide as defined above. After the transfer of the expression vector into the host cell/host organism one part of the host cells or host organisms are cultured in the presence of at least one candidate of an inhibitor- or activator-molecule and under culture conditions that allow the expression, preferably the overexpression of the RNA, peptide or polypeptide as defined above. The other part of the transfected host cells are cultured under the same culture conditions, but in the absence of the candidate of an inhibitor- or activator-molecule.

In another preferred embodiment, the screening method for the identification and characterization of an interacting molecule useful in the treatment and/or prophylaxis of Cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis from a library of test substances comprises the following steps:

-   -   a) recombinantly expressing a polypeptide encoded by a nucleic         acid molecule sequence as defined above in a host cell,     -   b) isolating and optionally purifying the recombinantly         expressed polypeptide of step (a),     -   c) optionally labelling of the test substances and/or labelling         of the recombinantly expressed polypeptide,     -   d) immobilizing the recombinantly expressed polypeptide to a         solid phase,     -   e) contacting of at least one test substance with the         immobilized polypeptide,     -   f) optionally one or more washing steps, and     -   g) detecting the binding of the at least one test substance to         the immobilized polypeptide at the solid phase.     -   h) performing a functional assay.         Step a) includes the recombinant expression of the above         identified polypeptide or of its derivative from a suitable         expression system, in particular from cell-free translation,         bacterial expression, or baculuvirus-based expression in insect         cells.         Step b) comprises the isolation and optionally the subsequent         purification of said recombinantly expressed polypeptides with         appropriate biochemical techniques that are familiar to a person         skilled in the art.

Alternatively, these screening assays may also include the expression of derivatives of the above identified polypeptides which comprises the expression of said polypeptides as a fusion protein or as a modified protein, in particular as a protein bearing a “tag”-sequence. These “tag”-sequences consist of short nucleotide sequences that are ligated ‘in frame’ either to the N- or to the C-terminal end of the coding region of said target gene. Commonly used tags to label recombinantly expressed genes are the poly-Histidine-tag which encodes a homopolypeptide consisting merely of histidines, particularly six or more histidines, GST (glutathion S-transferase), c-myc, FLAG®, MBP (maltose binding protein), and GFP. In this context the term “polypeptide” does not merely comprise polypeptides with the nucleic acid sequences as listed in Table 10 their naturally occurring homologs, preferably orthologs, more preferably human orthologs, but also derivatives of these polypeptides, in particular fusion proteins or polypeptides comprising a tag-sequence.

These polypeptides, particularly those labelled by an appropriate tag-sequence (for instance a His-tag or GST-tag), may be purified by standard affinity chromatography protocols, in particular by using chromatography resins linked to anti-His-tag-antibodies or to anti-GST-antibodies which are both commercially available. Alternatively, His-tagged molecules may be purified by metal chelate affinity chromatography using Ni-ions. Alternatively to the use of ‘label-specific’ antibodies the purification may also involve the use of antibodies against said polypeptides. Screening assays that involve a purification step of the recombinantly expressed target genes as described above (step 2) are preferred embodiments of this aspect of the invention.

In an—optional—step c) the compounds tested for interaction may be labelled by incorporation of radioactive isotopes or by reaction with luminescent or fluorescent compounds. Alternatively or additionally also the recombinantly expressed polypeptide may be labelled.

In step d) the recombinantly expressed polypeptide is immobilized to a solid phase, particularly (but not limited) to a chromatography resin. The coupling to the solid phase is thereby preferably established by the generation of covalent bonds.

In step e) a candidate chemical compound that might be a potential interaction partner of the said recombinant polypeptide or a complex variety thereof (particularly a drug library) is brought into contact with the immobilized polypeptide.

In an—optional—step f) one or several washing steps may be performed. As a result just compounds that strongly interact with the immobilized polypeptide remain bound to the solid (immobilized) phase.

In step g) the interaction between the polypeptide and the specific compound is detected, in particular by monitoring the amount of label remaining associated with the solid phase over background levels.

Such interacting molecules may be used without functional characterization for diagnostic purposes as described above.

In another aspect, the invention relates to a method for the preparation of a pharmaceutical composition wherein an inhibitor or activator of cell cycle progression is identified according to any of the screening methods described above, synthesized in adequate amounts and formulated into a pharmaceutical composition.

Suitable methods to synthesize the inhibitor or activator molecules are known in the art. For example, peptides or polypeptides can be synthesized by recombinant expression (see also above), antibodies can be obtained from hybridoma cell lines or immunized animals. Small molecules can be synthesized according to any known organic synthesis methods.

Similarly, said inhibitor or activator may be provided by any of the screening methods described above and formulated into a pharmaceutical composition.

Another embodiment of the invention is the use of the screening methods of the invention in the field of cardiovascular diseases, preferably disorders of lipid metabolism and atherosclerosis.

The following examples illustrate the present invention without, however, limiting the same thereto.

Unless otherwise specified, the manipulations of nucleic acids and polypeptides/-proteins can be performed using standard methods of molecular biology and immunology (see, e.g. Maniatis et al. (1989), Molecular cloning: A laboratory manual, Cold Spring Harbour Lab., Cold Spring Harbour, N.Y.; Amusable, F. M. et al. (eds.) “Current protocols in Molecular Biology”. John Wiley and Sons, 1995; Tijssen, P., Practice and Theory of Enzyme Immunoassays, Elsevier Press, Amsterdam, Oxford, N.Y., 1985).

EXAMPLES Example 1 Generation of dsRNA Molecules for RNAi Experiments

siRNA of a given siRNA sequence were synthesized by Ambion, Inc. (Austin, Tex., USA), using standard methods known to the person skilled in the art of siRNA synthesis.

Example 2 Cell Seeding and Transfection of Cells

Huh human hepatoma cells, cultivated in RPMI (Gibco/Invitrogen) medium containing 10% FBS, 1% non-essential amino acid solution (Gibco/Invitrogen), 1% Penicillin/Streptomycin solution (Gibco/Invitrogen), 1% Glutamine (Gibco/Invitrogen) and 1% Hepes pH 8 (Gibco/Invitrogen), were treated with siRNAs at a final concentration of 100 nM using a lipofection based transfection protocol.

24 h before transfection, Huh cells were disattached from the flask by incubation with 3 ml Trypsine solution (Gibco/Invitrogen) for 5 min at 37° C. Cells were harvested by adding 10 ml of RPMI medium to the flask. 4000 cells/well were seeded in black, optical 96well plates (Costar/Corning) in a volume of 100 ul/well. To allow homogenous settling of the cells, important for an even intra well distribution of the cells, the plates were left for 30 min at RT before they were transferred to an incubator with 37° C. and 5% CO₂.

On the day of transfection, for each siRNA the transfection mix was prepared as follows: 4 μl of a 10 μM stock of siRNA was diluted with 64 μl of Opti-MEM (Invitrogen Inc.), and 1.6 μl Oligofectamine transfection reagent (Invitrogen) were diluted with 9.6 μl of Opti-MEM. For complex formation, both solutions were gently mixed and incubated for 20 min at RT. Culture medium was removed from the cells and 80 μl of fresh medium ([DMEM, Invitrogen) were added, followed by addition of 20 μl of transfection mix to each of replicate 3wells per siRNA. Cells were incubated at 37° C. for 4 hours and 50 μl of fresh medium, supplemented with 30% fetal calf serum were added. 24 h after addition of the transfection mix the complete medium described above, was replaced by RPMI medium, containing 2% Lipoprotein deficient serum (LPDS) instead of the 10% FBS.

As an internal control and for intra plate normalization each 96 well screening plate, transfected with 88 different sample siRNAs contained the following 8 control wells: 2 wells with siRNAs directed against HMGCR, 2 wells against SQLE, 3 wells with unspecific control siRNAs sharing no complete sequence homology with any coding sequence in the human transcriptome and 1 well without any siRNA.

The 3 replicate wells, assayed per siRNA were situated on 3 different screening plates (inter plate triplicates).

Example 3 Primary Screen Cell Staining and Fluorescence Microscopy Based Screening Readout Cell Staining:

For a primary readout, the expression level of the LDL receptor (LDLR) was measured by an indirect assay, quantifying the amount of available receptor by the amount of internalized LDL. To this end, 48 h after transfection the supernatant was replaced by pre-warmed fresh Lipoprotein deficient RPMI medium containing 2% LPDS and 3 ug/ml LDL, labelled with the lipid dye DiI (LDL-DiI), supplemented with 1 ug/ml Hoechst for staining of cell nuclei. After an incubation period of 60 min at 37° C. with this staining solution, cells were washed with phosphate buffered saline containing MgCL2 and CaCL2 (PBS+) and fixed with 4% PFA for 30 min at RT.

Image Acquisition:

Cells were imaged using a fully automated fluorescence microscope from MDC (Molecular Devices Corporation, CA, USA). Per experimental well 6 fields with a dimension of approx. 2×1.5 mm were acquired using excitation/emission conditions, optimized to the spectral properties of the two chromophores, DiI and Hoechst.

Image Analysis:

To quantify the degree of LDL-DiI uptake, each image acquired in the DiI channel was subjected to an automated image analysis algorithm, programmed using the MetaMorph image analysis software (Universal imaging/MDC). In this algorithm, an adaptive intensity threshold was used to define and measure the area covered by LDL-DiI labelled objects. For each image, this area was normalized to the fraction of total image area covered by cells (cell density).

The normalized LDL-DiI measurements and the cell density values derived from each of the 6 fields for a given well were averaged to obtain two data points (LDL-DiI and cell density) per experimental well. All experimental data points were normalized to the corresponding control data points taken from wells treated with non-template siRNA on the same plate. Finally, the plate-normalized LDL-DiI and cell density data points from corresponding wells on the 3 replicate plates were averaged to genearate a single mean value and standard deviation.

Validation of Screening Method by Confirming Positive Control Genes

As an internal control and for intra plate normalization each 96 well screening plate, transfected with 88 different sample siRNAs contained the following 8 control wells: 2 wells with siRNAs directed against HMGCR, 2 wells against SQLE, 3 wells with unspecific control siRNAs sharing no complete sequence homology with any coding sequence in the human transcriptome and 1 well without any siRNA.

In addition to its function as positive control gene, SQLE was also part of the screened library, targeted by 3 different siRNAs. 2 of these 3 siRNAs, one of them being identical to the SQLE positive control siRNA, were confirmed as positive in the screen showing LDL-DiI uptake values of 348% and 522% of the corresponding unspecific control value. SiRNAs targeting HMGCR were not present in the screened siRNA library.

Example 4 Secondary Screen

Selection of siRNAs

All genes, for which at least one single siRNA showing an increase in LDL-DiI uptake of more then 300% as compared to the negative control had been found in pass1 were subjected to a second round of screening (pass2). To control for potential errors in the synthesis of the siRNAs used for pass1, all siRNAs used for pass2 were de nove synthesized. In addition to the siRNAs found positive in pass1, at least on additional siRNA with new sequence were tested for all genes found positive by only a single positive siRNA in pass 1.

Assay

Cell cultivation, seeding and transfection conditions as well as the choice of positive and negative control siRNAs, was identical between pass1 and pass2.

Differing from the staining conditions, described above for pass1, the uptake of fluorescently labeled transferrin was included as additional readout in pass2 to control for differences in the activity of receptor mediated uptake in general. To that end the staining solution described for pass 1 was supplemented with the soluble iron binding protein transferrin coupled to the fluorophore alexa488 (invitrogen) in a final concentration of 50 ug/ml. The staining procedure, image acquisition and image analysis was performed as described for pass1 with the only difference that alexa488 staining was imaged in a third channel, optimized to the spectral properties of the fluorophore alexa488. The intensity Transferrin-alexa488 staining was analyzed by the same intensity threshold based algorithm as used for the quantification of the LDL-DiI image data. Final readouts of the pass2 analysis were LDL-DiI uptake, cell proliferation and transferrin-alexa488 uptake.

Example 4 Third Pass Screening

Selection of siRNAs

The primary positive criterion for the selection of genes for a third round of analysis (pass3) was the level and the robustness of the increase in LDL-DiI uptake measured in pass 1 and 2. Preferably only genes with at least 2 positive siRNAs were selected. Negative criteria were a strong increase in transferrin uptake as well as a decrease in cell proliferation.

Assay

Cell cultivation, seeding and transfection conditions as well as the choice of positive and negative control siRNAs, was generally as described above for pass1 with the following differences:

Every siRNA, re-analyzed in pass3 was tested in a final concentration of 10 nM, 30 nM and 100 nM. The specific siRNAs were diluted with negative control siRNA solution such that the final total concentration of siRNA remained 100 nM.

In addition to the three wells, transfected with each siRNA and concentration for LDL-DiI and cell proliferation analysis another 3 wells were transfected for RT-PCR analysis of the knock down efficacy. Transfection for the functional assay and RT-PCR were done on separate experimental plates. For a better comparability all transfections were performed with the same transfection mix. To that end, the volume of the transfection mix generated for each siRNA and concentration as described above was doubled.

Final readouts of pass3 analysis were LDL-DiI uptake, cell proliferation and knockdown efficacy.

Validation of siRNA Efficacy by RT-PCR (qRT-PCR)

48-h after transfection total RNA was extracted from the cells using Invisorb 96 well kits (Invitek, Germany), following the protocol provided by the manufacturer. cDNA was synthesized using TaqMan RT reagents (Applied Biosystems, Foster City, Calif.) following the instructions provided by the manufacturer. Real-Time qPCR with gene-specific primers was performed in the following reaction mix

-   -   5.5 μl 2× SybrGreen PCR mix (ABgene, Surrey, UK)     -   3.0 μl cDNA     -   2.5 μl 2 μM primers     -   =11 μl total     -   in an ABI-7900-HT real-time PCR machine (Applied Biosystems)         running the following program:     -   50° C. 2 min-95° C. 10 min-45 cycles (95° C. 15 sec-60° C. 1         min)-95° C. 15 sec-60° C. 15 sec−95° C. 15 sec (melting curve).

In addition to expression of the gene of interest, expression level of GAPDH as a housekeeper was determined for each sample in order to account for inter-sample variability. The degree of knockdown was determined by comparing the amplification level for the gene of interest, normalized through the level of GAPDH, between samples transfected with a specific siRNA and samples transfected with unspecific control siRNAs.

Example 4 Determination of the Expression Level in HepG2, Huh, Primary Hepatocytes, and Whole Liver Cells

The expression levels of targets of the invention were determined using standard methods known to the person skilled in the art. Whereas it is not necessary to perform additional expression profiling experiments in order to practise the invention, some experimental details relating to the expression profiling experiments are provided for information purposes:

Preparation of total RNA was carried out using Trizole (Invitrogen) according to the manufacturer's instruction. The RNA quality was checked by gel-run and the integrity of ribosomal RNA bands using “RNA 6000 Nano Chips” from Agilent Technologies. Sample preparation for hybridization was performed using “Once-Cycle cDNA Synthesis Kit” (Affymetrix) followed by “Gene Chip Expression 3′-Amplification for IVT Labeling Kit” (Affymetrix). Gene Chip Scanner 3000+equipment (Affymetrix) and human Gene Chips “HG-U133 Plus 2” (Affymetrix) were used for signal detection. Signals were analyzed primarily using GCOS software (Affymetrix) and subsequently with GeneData software.

Expression level data are shown in table 4.

Example 5 Screening for Compounds Useful in the Treatment and/or Prophylaxis of Atherosclerosis Using a Cell Based Assay

The screening method for the identification of agonists or antagonists of the human cysteinyl leukotriene receptor 2 (CysLTR2; NM_(—)020377) using a cell based assay will be taken as an example.

The recombinant CHO-K1(ATCC No.: CCL-61) screening cell line expresses constitutively the calcium sensitive photoprotein Aequorin. After reconstitution with its cofactor Coelenterazin and increasing intracellular calcium concentration Aequorin is able to emit light (Rizzuto R, Simpson A W, Brini M, Pozzan T.; Nature 358 (1992) 325-327). Additionally, after transfection with a recombinant expression plasmid containing the full length cDNA for human CysLTR2, the screening cell line is stably expressing the CysLTR2 protein (Heise et. al., JBC 275 (2000) 30531-30536). The CysLTR2 screening cell line is able to react on stimulation with known CysLTR2 agonists (i.e. Leukotriene D4 and Leukotriene C4) with an intracellular Ca⁺⁺ release and resulting luminescence can be measured with appropriate luminometer (Milligan G, Marshall F, Rees S, Trends in Pharmacological Sciences 17 (1996) 235-237). Preincubation with CysLTR2 antagonists diminish the Leukotriene D4 or Leukotriene C4 induced Ca⁺⁺ release and consequently the resulting luminescence.

Cells were seeded into 384 well cell culture plates and preincubated for 48 hours in culture medium (DMEM/F12 with Glutamax, Gibco Cat.# 61965-026; 10% Fetal Calf Serum, Gibco Cat.# 10270-106; 1.4 mM Natriumpyruvat, Gibco Cat.# 11360-039; 1.8 mM Natriumbicarbonate, Gibco Cat.# 25080-060; 10 mM HEPES, Gibco Cat.# 15290-026) under standard cell culture conditions (96% humidity, 5% v/v CO₂, 37° C.). Culture medium is replaced by Tyrode buffer (containing 140 mM NaCl, 5 mM KCl, 1 mM MgCl₂, 2 mM CaCl₂, 20 mM Glucose, 20 mM HEPES) plus Coelenterazin (50 μM) and incubation is continued for additional 3-4 hours. Reference agonists Leukotriene D4, Leukotriene C4 or putative agonists are added to the cells and luminescence is measured subsequently. For antagonist screening, 15 min preincubation with putative antagonists is allowed before Leukotriene D4 (3×100⁻⁸ M) stimulus.

Example 6 Screening for Compounds Useful in the Treatment and/or Prophylaxis of Atherosclerosis Using a Cell-Free Assay

The screening method for the identification of inhibitors of the human Phosphodiesterase 4B (PDE4B; NM_(—)002600) using a cell-free biochemical assay will be taken as an example. PDE4B (GenBank/EMBL Accession Number: NM_(—)002600, Obernolte et al. Gene. 1993 129, 239-247) was expressed in SD insect cells using the Bac-to-Bac™ baculovirus expression system. Cells were harvested 48 h after infection and suspended in lysis buffer (20 ml/1 l culture, 50 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM MgCl2, 1.5 mM EDTA, 10% Glycerin, 20 μL protease in-hibitor cocktail set III [CalBiochem, La Jolla, Calif. USA]). The cells were disrupted by sonication at 4° C. and cell debris were removed by centrifugation at 15,000×g at 4° C. for 30 minutes. The supernatant is designated PDE4B cell extract and is stored at −80° C.

For determination of the in vitro effect of test substances on the PDE4B reaction, test substances are dissolved in DMSO and serial dilutions in DMSO are performed. 2 μl of the diluted test compounds are placed in wells of microtiter plates (Isoplate; Wallac Inc., Atlanta, Ga.). 50 μl of a dilution of the PDE4B cell extract (see above) is added. The dilution of the PDE4B cell extract will be chosen that during the incubation with substrate the reaction kinetics is linear and less than 70% of the substrate is consumed (typical dilution 1:150 000; dilution buffer: 50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA, 0.2% BSA). The substrate, [5′,8-3H] adenosine 3′,5′-cyclic phosphate (1 μCi/μl; Amersham Pharmacia Biotech., Piscataway, N.J.) is diluted 1:2000 in assay buffer (50 mM Tris/HCl pH 7.5, 8.3 mM MgCl2, 1.7 mM EDTA). The reaction starts by addition of 50 μl (0.025 μCi) of the diluted substrate and incubates at room temperature for 60 min. The reaction is stopped by addition of 25 μl of a suspension containing 18 mg/ml yttrium scintillation proximity beads in water (Amersham Pharmacia Biotech., Piscataway, N.J.). The microtiter plates are sealed, left at room temperature for 60 min, and are subsequently measured in a Microbeta scintillation counter (Wallac Inc., Atlanta, Ga.). IC50 values will be determined by plotting the substrate concentration against the percentage PDE4B inhibition.

TABLE 1 Target siRNA Proliferation No. ID LDL-Dil Mean % Mean % Target Class(es) Target symbol 1 113613 724.0965615 107.8625974 Protein kinase, Protease ANKRD3 1 105742 557.2013279 129.7804577 Protein kinase, Protease ANKRD3 1 105202 426.5918541 119.7514464 Protein kinase, Protease ANKRD3 2 117853 579.7551381 125.5260757 Other enzyme HLCS 2 117852 374.3721807 84.77067934 Other enzyme HLCS 2 117851 348.0013938 110.6440668 Other enzyme HLCS 3 117417 447.7431016 113.882518 Membrane protein, Cytochrome P450 SC4MOL 3 117416 399.631074 108.1712372 Membrane protein, Cytochrome P450 SC4MOL 3 117418 397.3576822 102.42365 Membrane protein, Cytochrome P450 SC4MOL 4 42711 527.9275211 88.0695743 Protease CASP1 4 42626 365.2281846 105.920996 Protease CASP1 5 10418 413.9186256 93.80525184 Other enzyme CDC42 5 10505 332.8978976 102.4573283 Other enzyme CDC42 6 118135 361.0739928 86.00868898 Ion channel, Other enzyme ABCC2 6 116839 342.4148736 132.2113457 Ion channel, Other enzyme ABCC2 7 105039 937.1680485 122.6094906 Protease CTSE 7 105041 328.0440766 113.0076858 Protease CTSE 8 1147 501.3206562 107.3294904 Protein kinase FRK 8 1243 377.3780055 110.0406079 Protein kinase FRK 9 8225 395.3088334 105.3314627 Other enzyme HMBS 9 117844 386.5308856 79.21133011 Other enzyme HMBS 10 106087 551.4313155 88.44182963 Transporter, Other enzyme HSD17B4 10 106089 400.7479977 107.44149 Transporter, Other enzyme HSD17B4 11 121011 383.0979608 99.41485592 Transporter LCN2 11 121012 366.9633728 131.659559 Transporter LCN2 12 1766 723.8356377 107.0417947 GPCR OXTR 12 1947 444.0141863 115.0667872 GPCR OXTR 13 142836 377.9953683 127.8244045 Phosphatase PPP1R3C 13 142834 339.4652831 105.2028745 Phosphatase PPP1R3C 14 1547 478.2634431 133.7832329 Protein kinase MAPK9 14 1452 319.9391015 124.7111395 Protein kinase MAPK9 15 1699 499.9106861 111.7567033 Protein kinase MAP2K5 15 118252 403.7219125 105.1834443 Protein kinase MAP2K5 16 43916 322.0473129 131.2710631 Other enzyme TPI1 16 43820 321.2912134 119.4372173 Other enzyme TPI1 17 402 471.3653067 123.3723017 Protein kinase VRK1 17 401 386.3750915 134.9480071 Protein kinase VRK1 18 117695 457.7827807 107.5940504 Ion channel SLC30A2 18 117693 425.8395112 102.8000404 Ion channel SLC30A2 19 118261 747.4553015 106.336687 Protein kinase ULK1 19 118260 445.9651692 108.8989791 Protein kinase ULK1 20 5146 478.40008 117.5601535 GPCR GLP2R 20 5237 451.8708414 104.3488796 GPCR GLP2R 21 828 343.2595327 113.2848132 Protein kinase SNK 21 829 340.2448823 102.9484122 Protein kinase SNK 22 19104 538.6343597 77.27418771 Protease SPUVE 22 19196 464.0190864 86.22550377 Protease SPUVE 23 103354 389.1368559 101.8826824 Protein kinase PASK 23 978 367.9530516 119.4915761 Protein kinase PASK 24 2240 527.5919554 97.51493592 GPCR OR52A1 24 2061 397.4248924 112.9250133 GPCR OR52A1 25 20115 671.5714404 104.2916365 Other RGS17 25 20024 623.6859075 95.18970662 Other RGS17 26 118397 407.9391857 120.1308385 Other enzyme MYLIP 26 118398 372.3127731 119.6270998 Other enzyme MYLIP 27 104835 524.0586705 102.0993329 Ion channel PKD1L2 27 104830 339.3777111 115.0438781 Ion channel PKD1L2 28 119221 1232.307505 120.3077073 Other enzyme BPHL 29 105141 1135.645376 111.8054786 Protease USP3 30 122236 1130.561627 109.6859813 Other enzyme NCE2 31 43781 1039.484616 117.1937166 Ion channel KCNK17 32 103636 1008.035233 80.27430588 Protein kinase WEE1 33 45922 995.1241621 107.4914643 Ion channel KCNE1 34 117371 961.5218898 104.0451117 Membrane protein RNUT1 35 111157 911.0548065 118.3141676 Receptor, Transporter M6PR 36 38979 909.6821061 112.7311274 Other enzyme MGC39650 37 121933 894.7821748 109.4947078 Metabolic kinase FLJ22761 38 119829 883.6759642 125.6237574 Other enzyme PAPOLG 39 19471 880.6891857 105.2230754 Other enzyme DNM1L 40 120442 872.601332 113.0064783 Other PSMD14 41 105154 868.7484538 109.3678977 Membrane protein, Protease BACE 42 6196 862.0651883 81.97030552 GPCR FKSG79 43 105753 815.426425 112.004123 Extracellular Factor, Protease LCN7 44 21895 783.7479458 92.43528375 Other STARD8 45 120445 771.9380665 107.8213079 Metabolic kinase RASGRP2 46 111807 757.3894801 123.5997027 Protease QPCT 47 1721 750.0679293 124.7542444 GPCR ADORA1 48 1774 742.4680415 110.8603652 GPCR TACR1 49 117712 732.0427107 99.03670761 Metabolic kinase ABCA10 50 1795 717.9672016 111.0300467 Other enzyme, GPCR GPR56 51 117084 717.0543713 98.15556498 Metabolic kinase PRPSAP2 52 119926 702.3467999 112.1197297 Other SLC26A10 53 9067 701.3622509 101.2032536 Other enzyme ADH7 54 121179 694.363976 99.0917368 Transporter OBP2A 55 38327 691.601585 110.4531546 GPCR MRGX1 56 111813 690.4898311 101.6885907 Receptor TNFRSF13B 57 107569 685.2375591 113.0692617 Other enzyme TP53I3 58 10560 683.6891137 119.9488634 Extracellular Factor, Protease CPB2 59 10235 674.784399 103.4678804 Other enzyme ARFD1 60 104127 671.3189247 124.5246892 Membrane protein, Protease ADAM29 61 112077 669.0628066 106.5058056 Membrane protein, Other enzyme AGPAT3 62 105010 667.8419405 115.448212 Protease CTSK 63 4154 666.2737834 115.6483854 GPCR GPR39 64 40980 665.0042604 115.2723859 Protein kinase TTBK 65 120756 657.8375343 98.83391855 Ion channel, Other enzyme ATP2A3 66 1627 657.6377629 110.8290477 Protein kinase FYN 67 122128 654.5962745 94.78045661 Other C20orf185 68 2207 652.1480701 108.8107556 GPCR HM74 69 4633 648.8978572 109.3070437 GPCR TRHR 70 119952 643.060823 111.3827969 Ion channel SLC12A2 71 105325 639.0989022 117.6878074 Protease CPA3 72 112330 638.5537811 112.097435 Membrane protein, Other enzyme D4ST1 73 121576 637.0982295 111.5476447 Other APC2 74 117799 634.8557057 95.77884911 Membrane protein, Transporter MGC52019 75 104458 623.4163967 109.9925709 Ion channel VDAC2 76 112453 621.914958 104.8333388 Other enzyme OGT 77 121337 620.1229465 76.02226238 Other CENPE 78 110844 616.8572379 107.0996448 Protein kinase BCR 79 119422 615.5313864 124.7454668 Other ARHGEF1 80 119276 611.4653566 116.6563534 Other enzyme VCP 81 118817 607.1952205 114.8743124 Other enzyme MCCC1 82 118114 604.2286536 109.025425 Other enzyme FKBP7 83 118462 603.7820058 116.0990749 Other enzyme KIF13B 84 46510 602.1553771 117.4146548 GPCR TG1019 85 119129 596.6163895 99.86760244 Other enzyme CRMP1 86 119399 596.5066921 108.1484036 Membrane protein ELOVL3 87 122166 596.0888651 123.6677082 PDE, TF APEX1 88 45063 595.5817158 108.7972263 GPCR GALR2 89 117601 591.648211 101.7554096 Ion channel SLC12A9 90 118446 586.7366596 87.23668446 Other enzyme KIF2C 91 18240 585.1080767 150.6046065 Other enzyme FTCD 92 104559 583.2891731 93.57598288 Ion channel CACNA2D2 93 1407 582.6120269 107.4681385 Protein kinase MAPK14 94 119077 580.3892176 107.480239 Other enzyme HEXA 95 1371 579.6300222 118.6112653 Metabolic kinase SPHK1 96 106537 576.8755334 108.3728865 Ion channel, Other enzyme ATP5J 97 120500 569.7068059 109.7162037 Protease POLG2 98 111654 569.0455244 89.29363902 Receptor CSF2RA 99 118718 568.5187083 140.2249957 Other SERPINB9 100 120608 566.5601546 96.91618938 Other enzyme UBASH3A 101 142253 565.0705142 96.60817895 Other PPP1R7 102 111081 561.6549265 105.5657572 Protein kinase HIPK1 103 103786 561.4171922 106.9513773 Metabolic kinase GUK1 104 121943 560.3439799 121.3027078 Other enzyme C2orf8 105 121806 558.8248481 102.018319 Other ITLN1 106 15527 555.5907735 113.5415583 PDE PDE1A 107 143005 554.7628422 96.54027294 Other PKIA 108 110607 554.5198986 113.1832064 Receptor GHR 109 107834 553.9818333 109.131078 Other enzyme AASS 110 121163 551.6493273 91.0952295 LOC339133 111 118522 547.5230683 96.41671994 Other KIAA0449 112 120179 540.9753304 113.9270416 Other enzyme UBE3A 113 34999 538.7824646 105.9660181 Membrane protein FLJ14681 114 6091 535.7500463 117.4985747 GPCR GPR84 115 103829 534.428009 104.0677126 LOC374425 116 119396 529.5612528 129.9072277 Other ARHGEF7 117 8816 528.2010911 75.09671631 Phosphatase SMPD1 118 15339 523.459779 118.0882192 Other AKAP5 119 29459 521.6044998 124.3187155 Protease, GPCR FLJ21839 120 16059 520.3864804 104.3274648 Other enzyme PDHA2 121 104173 516.8720868 109.2701396 Membrane protein, Protease ADAM19 122 120611 514.8446941 98.9901288 Other enzyme RAB25 123 142929 514.641299 114.9158966 Other enzyme PRKAB1 124 35220 513.79528 109.7998872 PDE CNP 125 119469 512.6228606 102.7033106 Other GCHFR 126 121471 512.2218386 88.8904603 Other BCL10 127 122003 511.1386983 117.9098859 Other enzyme CTMP 128 114058 501.7929708 108.376556 Membrane protein APP 129 117031 499.8903038 128.6630551 Other enzyme GLRX 130 110906 499.0068257 99.27448263 Receptor CXADR 131 119517 496.4590532 107.397945 Metabolic kinase PRPS1L1 132 114048 496.432642 104.5733205 Extracellular Factor PROS1 133 809 496.0368444 109.2690557 Receptor, Protein kinase MERTK 134 137195 492.7135544 97.82416987 Membrane protein, Transporter STX10 135 118341 489.8746301 106.0839193 Other Dlc2 136 46319 488.5824125 107.5095504 TF, Other enzyme KLP1 137 7204 488.1470659 118.6782488 Ion channel KCNN4 138 119081 487.2951811 117.7883959 Other enzyme MAN2B1 139 745 486.0636832 111.7504375 Protein kinase STK10 140 119216 483.9639174 115.4574626 Membrane protein, Other enzyme BCS1L 141 117277 482.0554412 110.68092 Ion channel SLC22A14 142 14775 481.7919942 127.2075723 Ion channel, Other enzyme NDUFA1 143 119182 481.2601456 108.4484729 Other SCP2 144 1286 480.4428342 143.2857253 Metabolic kinase FLJ22055 145 1961 480.3311394 107.9689303 GPCR GPR1 146 119782 478.1125004 117.7041399 Other enzyme ADARB1 147 135366 477.8044802 101.0742182 Receptor, Other enzyme C20orf41 148 42362 477.3018528 116.0371527 GPCR OPN1LW 149 12155 475.4036511 103.5565493 Receptor PVRL2 150 11 472.1435798 129.4741064 Receptor, Protein kinase ACVRL1 151 7881 470.7065238 105.5885503 Protease CAPN3 152 10428 470.1389417 103.1033828 Other enzyme ARF4 153 16123 468.9022491 112.8774241 Other enzyme HADHSC 154 1049 468.8637745 129.5102382 Protein kinase CLK4 155 919 468.8403522 110.1488223 Protein kinase IKBKE 156 121066 465.8888922 108.6829237 Membrane protein, Transporter PLSCR3 157 105169 465.65 109.56 Protease CAPN7 158 36311 461.5506217 101.7180979 Other RGS18 159 5884 460.9703523 100.2741634 Extracellular Factor, GPCR GPRC5D 160 44940 460.1503308 117.9056609 Extracellular Factor, Other enzyme SOD3 161 1398 459.3250946 112.682103 Protein kinase KIS 162 104626 459.0052531 106.500977 Ion channel SCN8A 163 15563 458.1980207 99.48194892 Other CCM1 164 136772 455.6291794 112.5796027 Protease MAPK8IP3 165 46183 455.0369741 95.40698084 Membrane protein, Other enzyme DDX19 166 5377 454.3248519 102.7635827 NHR PPARD 167 103491 453.9228137 104.860333 Protein kinase MAP3K6 168 117929 453.4469364 124.9105413 Ion channel, Other enzyme ATP5L 169 110591 452.1013707 99.46085555 Other enzyme CPT2 170 103534 450.854997 99.55271092 Metabolic kinase UCK1 171 119066 448.5023269 116.4950259 Other enzyme PAFAH2 172 106403 447.7355841 103.1864783 Other enzyme ALDH7A1 173 121059 443.7782504 121.3182105 Membrane protein, Other enzyme NLGN3 174 121219 443.7626772 95.08540306 Other enzyme AGA 175 117366 441.8016351 112.146955 Receptor, Transporter, Other enzyme ABCC9 176 105936 441.7006486 123.6696823 Other enzyme BCKDHB 177 105919 441.4001365 91.29145842 Other enzyme ACYP2 178 103932 440.2236799 108.4298231 Receptor, Protease CRN 179 43139 440.0553435 112.0568553 GPCR VN1R2 180 9108 439.4782496 97.36939074 Other enzyme GAD2 181 111592 439.2244568 94.54135852 Membrane protein, Other enzyme UST 182 104388 438.7260273 102.5332305 Ion channel CLCN3 183 115931 437.8127994 135.1133409 Membrane protein, Transporter SLC7A8 184 30832 437.5023782 105.2856129 Receptor LENG4 185 105076 437.17 117.45 Protease USP13 186 44885 436.7502954 114.8286775 Transporter FABP6 187 103580 436.062396 108.1960182 Protein kinase MAP2K4 188 1555 435.5537573 109.605547 Receptor, Protein kinase EPHA5 189 105163 435.31 109.22 Protease USP25 190 105773 435.0740598 144.0864242 Membrane protein, Other enzyme GGTL3 191 37190 434.0342172 88.66505884 ion channel TPCN2 192 121953 430.5466199 105.0355231 Other NIPA2 193 9040 430.2437962 95.25449892 Receptor ITGAX 194 119716 429.962131 117.0526368 Membrane protein, Other enzyme GCS1 195 1794 429.7748549 110.2235499 GPCR SMO 196 115136 426.3537874 120.697878 Membrane protein BTNL3 197 116921 426.3489396 103.3179972 Ion channel SLC6A4 198 117213 424.9317649 114.6683856 Ion channel, Other enzyme ATP6V0B 199 10426 424.6800256 100.6599002 Other enzyme ARF1 200 657 424.2803144 110.0707016 Protein kinase FER 201 46002 424.0998283 106.3030606 Other CST4 202 105830 423.9794398 132.1654218 Phosphatase PPP1CC 203 104815 422.7271262 108.4054772 Ion channel KCNK16 204 142280 422.4332159 117.4788526 Other PRKAR2B 205 1940 422.2064234 111.9069403 GPCR HTR2C 206 103397 421.7134033 103.2349516 Receptor, Protein kinase PRKCM 207 117187 421.3769777 89.26506104 Membrane protein, Other enzyme AOC3 208 119405 419.7767205 115.1077039 Other RALGPS2 209 111208 419.5450302 111.3857744 Receptor PVRL1 210 118568 419.5080913 110.2725123 Other enzyme SUOX 211 383 417.6612083 110.276135 Protein kinase TEC 212 118038 417.4594611 98.91886222 Other enzyme NPL 213 42454 417.4525613 136.8225457 Membrane protein BCL2L10 214 118423 417.3833267 113.9351218 Other KIF2 215 104231 415.5472125 122.6465741 ADAMTS6 216 121036 414.2913367 112.0586636 Phosphatase OBDPF 217 5834 413.6532193 107.9929627 Extracellular Factor, GPCR GPRC5B 218 114204 412.0637499 108.3105401 Other enzyme GLUL 219 119258 411.550307 123.7394163 Other enzyme DPYSL4 220 111728 410.8622342 107.615019 Receptor LILRB5 221 119072 410.7692094 112.7932252 Other enzyme GALNS 222 121053 410.6748168 125.8988577 Other enzyme FLJ10948 223 142803 408.4220781 111.9784737 Other PRKRIR 224 117248 407.8600302 109.1391643 Membrane protein, Other enzyme PIGL 225 111369 406.8963067 117.544814 Receptor TNFRSF14 226 118232 406.0702778 110.9422262 Protein kinase, TF ATM 227 10238 404.4325747 102.5970025 Other ARF3 228 118663 404.1548174 110.3151909 Protease SERPINB2 229 13014 402.3581073 105.059737 Other VAV2 230 118922 401.7314201 125.7291744 Membrane protein, Other enzyme CA14 231 119792 401.5504069 112.8674237 Extracellular Factor, Receptor TRAP1 232 103447 401.4657662 113.3929041 Protein kinase CAMK1G 233 23376 400.903468 129.3779453 Protease LAP3 234 17099 400.6668315 121.5410914 Other enzyme MDH2 235 138240 399.8410482 102.9862625 Extracellular Factor, Other enzyme PRKCABP 236 9004 399.0331463 105.8619609 Extracellular Factor CRH 237 1785 398.6434209 116.8090635 GPCR GPR3 238 107446 397.8207756 101.3664701 Ion channel, Other enzyme NDUFA10 239 108267 397.8059949 113.9873132 Receptor C1QR1 240 122036 397.8001642 113.3477815 Other FLJ32389 241 118553 397.6307055 105.0768078 Extracellular Factor SERPINA7 242 119612 397.6118587 98.7004085 Other enzyme DCTD 243 121775 397.5898454 117.3560989 Extracellular Factor ANGPTL4 244 110854 397.3658168 82.32707254 Membrane protein, Protein kinase DCAMKL1 245 126062 396.7226181 116.1216962 Phosphatase FLJ23751 246 118792 396.7068231 121.4933783 Other enzyme BIA2 247 120597 396.6975195 138.6302845 Other enzyme HDAC8 248 119183 396.3604372 109.938439 Other enzyme UPP1 249 121277 395.9619555 100.6813608 Other enzyme ANG 250 117497 395.0172017 96.78517027 Ion channel SLC39A2 251 1704 394.8804771 109.210148 Metabolic kinase PANK1 252 119905 394.0107872 145.6705418 Membrane protein, Transporter SLC25A11 253 121507 391.1060844 95.47181587 Other enzyme DDX21 254 121103 390.9844878 117.1793186 Other enzyme CACH-1 255 6501 390.7851321 110.5802459 GPCR ADRA1D 256 43395 390.66731 115.7281563 Membrane protein, Other enzyme NLGN4Y 257 1541 390.469141 109.3497418 Protein kinase, GPCR PDGFRB 258 648 389.0628479 104.4644251 Receptor, Protein kinase EPHA1 259 22653 388.9007577 98.13047718 Other CENTD2 260 112041 388.5370327 114.1528932 Other enzyme AD-017 261 116939 388.4574861 107.1931501 Other enzyme ACLY 262 111049 387.2108178 103.2891867 Metabolic kinase FUK 263 120730 386.988569 124.866649 Other RHEBL1 264 1776 386.8180132 88.58584251 GPCR ADCYAP1R1 265 139134 386.3029721 118.0988203 Metabolic kinase PIP5K1B 266 118865 386.072946 113.9593622 Other SERPINB11 267 119034 384.48802 120.2533328 Other enzyme GCH1 268 41802 384.3933062 114.8527283 Membrane protein, Other enzyme UGT2B11 269 115614 383.0489224 108.3278972 TF ATF1 270 120142 382.7535652 106.4879167 Ion channel SLC39A4 271 129420 382.5683087 101.9266991 Metabolic kinase PIK3AP1 272 35139 381.7248731 129.8871627 Other enzyme LDHL 273 112237 381.5310991 121.4406138 Other enzyme AGXT2L1 274 118332 381.2599671 116.1870781 Other DNCLI1 275 202390 381.0330204 114.3109014 Membrane protein, Other enzyme HS3ST4 276 111442 379.6241977 116.4321259 Membrane protein, Other enzyme CHST2 277 119734 379.4911971 96.99996658 Other enzyme GNA13 278 46555 379.0545062 108.3805591 Other MGC30208 279 112493 378.5408605 89.61741639 Membrane protein, Other enzyme GALNT10 280 120542 378.1641943 103.8492052 Other enzyme NEDL1 281 143975 377.9499383 131.2863056 Metabolic kinase PIK3CD 282 202509 377.8694154 97.95793669 Protein kinase KIAA0551 283 26615 376.8374238 103.2283291 Other enzyme RHOT1 284 2021 376.5797096 132.656305 GPCR MTNR1B 285 1017 376.156958 114.0562439 Protein kinase FLJ10074 286 44902 375.5435041 106.7019829 Other enzyme GAPD 287 121821 374.6192962 123.4205013 GPCR C20orf12 288 3573 373.9255838 112.1625485 TF TRIM16 289 111379 373.9111692 92.20755942 Receptor TNFRSF10C 290 119725 373.7070491 123.9564273 Other enzyme RPC32 291 119012 373.7018113 113.7521602 Other enzyme ARSE 292 11202 373.6632911 115.5299636 Receptor ITGB8 293 119352 372.7179192 113.6092933 Other enzyme DPYSL5 294 111028 372.5956763 104.5128705 Protein kinase MARK4 295 6242 372.0353982 101.495524 GPCR P2RY12 296 6829 371.9102091 113.1570297 GPCR GPR113 297 120986 370.5294104 94.75769169 Other PLIN 298 282 370.3960758 116.4681362 Metabolic kinase PIK4CB 299 119249 369.9428144 113.4634652 Other RAPGEF3 300 121002 369.8711654 116.7251919 Transporter RBP2 301 112098 369.5515149 128.5647748 Membrane protein, Other enzyme LOC57168 302 120006 369.3823539 107.6925684 Ion channel SLCO1B1 303 9145 369.3015495 102.517714 Phosphatase PLCB3 304 45672 369.0790566 108.3570787 Other ASB10 305 5997 368.5900838 116.6606331 GPCR MC3R 306 5922 368.0630501 122.4474375 NHR NR2F2 307 112027 367.9815221 98.60310902 Membrane protein, Other enzyme LPAAT-e 308 42079 367.8448019 100.7261083 Ion channel KCNJ4 309 104120 366.9358617 128.2650179 Membrane protein, Protease ADAM18 310 104465 366.3929912 113.6588387 Ion channel, Other enzyme KCNAB2 311 118241 365.9321943 106.4669235 Metabolic kinase NME3 312 12487 365.5328622 124.7024867 Other enzyme SMARCA3 313 139155 365.2402515 95.96747073 Membrane protein, Transporter STX7 314 7014 365.2343599 105.1510693 Ion channel CLCN5 315 107742 365.1722202 121.6315236 Membrane protein, Other enzyme HSD11B1 316 122070 363.9494025 97.98606684 Other ARHGEF19 317 119167 363.5067705 132.3645072 Membrane protein, Other enzyme LCT 318 121082 363.4719077 123.18997 Ion channel SFXN1 319 34166 362.4141694 111.3714375 Metabolic kinase CARD11 320 36798 361.9815571 94.43917848 Other enzyme LYPLAL1 321 6764 361.5881078 116.6719888 GPCR MRGX2 322 112281 361.211568 104.7476966 Receptor HAVCR2 323 1359 360.6229671 109.7421686 Protein kinase DKFZp761P1010 324 120792 360.1322955 119.6152026 Ion channel, Other enzyme ATP6V1E1 325 120227 359.5034833 136.1347787 Ion channel, Other enzyme ATP2B1 326 117144 359.037843 84.88109411 Other enzyme UAP1 327 202463 358.8380192 105.8085832 Metabolic kinase LOC375133 328 326 358.400703 108.0356713 Protein kinase MAP2K1 329 121132 358.0920934 124.2705074 Receptor ITGA1 330 40762 357.9844049 129.9341867 Protein kinase SNF1LK 331 106985 357.0935603 116.5846304 Cytochrome P450 SPR 332 118634 357.0098956 112.4279362 Other CCNF 333 1709 356.536362 114.2935848 GPCR AVPR2 334 119230 354.9303323 100.1501686 Other ARHGEF2 335 111644 354.8077797 119.2212102 Membrane protein, Other enzyme SIAT10 336 103331 354.3918817 107.4194451 Receptor, Protein kinase ERBB4 337 105105 353.6602154 122.3410109 Protease BAP1 338 6671 353.5108852 115.217319 GPCR CD97 339 117749 352.7265894 128.6629429 Other enzyme FLJ30473 340 104678 352.5167014 112.8467449 Protein kinase, Ion channel TRPM7 341 4236 352.3335634 110.0391798 GPCR P2RY1 342 119150 352.2135679 114.6078946 Other enzyme APOBEC1 343 120536 352.1285019 92.66377649 Protease USP34 344 4084 351.6370776 117.7994424 GPCR CNR1 345 8584 351.4439648 123.2153662 Other enzyme RAG1 346 118025 350.756329 106.4389061 Other enzyme FLJ21963 347 104025 350.4577675 107.774929 Extracellular Factor, Protease MMP13 348 142304 350.2300498 105.844301 Protein kinase MAPK3 349 119004 349.6278446 121.9397977 Other enzyme FLJ23322 350 112199 349.199572 122.4161424 Membrane protein, Other enzyme CHST5 351 140383 348.776124 139.6400449 Membrane protein, Phosphatase MIR16 352 43202 348.6681287 102.831723 Other LOC134285 353 118558 348.1809774 108.7933859 Membrane protein, Cytochrome P450 TYR 354 122033 346.9686784 105.2816898 Other BIN1 355 110947 346.599087 100.2355326 Receptor GFRA3 356 122374 346.4990721 118.5241141 Other CALML3 357 121768 346.4657572 121.6190857 Membrane protein HMP19 358 110667 346.3715528 119.2857178 Membrane protein, Other enzyme UGT1A1 359 119683 346.0605729 116.9674912 Other SLC9A3R1 360 105368 345.9569033 115.4178217 Membrane protein, Protease MBTPS2 361 117476 345.8722247 105.0576544 Ion channel SLC30A4 362 8110 345.8696274 68.11996579 Protease PLG 363 108254 345.5531839 104.001058 Extracellular Factor, Receptor PLA2R1 364 119254 345.1450824 112.4167696 Other enzyme POLD2 365 120528 345.139316 114.9820103 Ion channel, Other enzyme ATP2C1 366 114721 345.0744395 113.4585363 TF, Protease SUPT16H 367 120404 344.600459 101.6414074 Other enzyme ARHI 368 121560 344.3589134 88.96359657 Other ARPC4 369 8759 343.7750672 101.211582 Extracellular Factor, Transporter ORM1 370 121689 342.7532716 94.90392556 Other C4.4A 371 116959 342.7449346 103.7426412 Transporter CLNS1A 372 18269 342.5183985 120.5404591 Membrane protein, Other enzyme MAN1A2 373 4118 342.2340458 112.4560621 Cytochrome P450 CYP2F1 374 120313 342.1408384 109.1143318 Other enzyme UBE2E1 375 14778 342.0333685 103.8887697 Ion channel, Other enzyme NDUFB2 376 1554 340.9120072 146.1444041 Protein kinase CDKL1 377 120581 340.6051973 108.7843543 Other enzyme RRAGB 378 135789 340.4662845 108.5254447 Other AKAP3 379 104313 340.3715661 136.4855116 Extracellular Factor, Ion channel GLRA1 380 5020 340.1495923 100.9024863 GPCR PNR 381 103787 339.8383981 121.4124757 Protein kinase MAP3K11 382 38222 339.806784 120.1618953 Receptor GFRA4 383 119010 339.6060599 103.7237111 Other enzyme ARSB 384 119464 339.4754061 100.5008021 Other enzyme TXNL 385 111967 339.2763036 112.4119069 Receptor SH120 386 117597 339.238818 111.3546779 Ion channel SLC6A20 387 616 339.1783001 110.5612083 Metabolic kinase PIP5K2A 388 104271 338.7413424 131.7387006 Extracellular Factor, Protease PLAT 389 41648 338.7181328 115.2805567 GPCR GPR38 390 116760 338.1994712 104.0012206 TF CREB5 391 103742 338.1738446 95.33904505 Protein kinase NEK8 392 121625 338.1483829 117.8622144 Other FAF1 393 108793 337.9238774 121.4085775 Membrane protein, Other enzyme RDH11 394 46149 337.8978345 120.3236494 Other enzyme PIN4 395 121965 337.8789473 113.6213753 Other BBP 396 104655 337.8013677 115.5912144 Phosphatase PTP4A1 397 3025 337.7404873 105.0254455 TF VAV1 398 23439 337.6708292 105.1774448 Extracellular Factor, Other enzyme PLA2G3 399 31620 337.1286426 124.1367317 Other FLJ22655 400 4069 336.8306941 105.5590406 GPCR BAI1 401 107669 336.303118 118.2304844 Receptor GFRA1 402 9248 336.0810213 122.0831997 Cytochrome P450 POR 403 106198 335.9733958 105.6352148 Other enzyme ALDH3A1 404 112515 335.9637286 119.3357808 Membrane protein RARRES1 405 8537 335.3533595 121.335137 Membrane protein, Transporter AQP1 406 110610 335.3244422 106.7081378 Extracellular Factor, Other enzyme GPI 407 43265 335.2808598 116.2065732 Membrane protein, Phosphatase PPAP2C 408 180 335.1659998 114.9252844 Protein kinase CSNK1A1 409 117634 334.7917391 105.1004972 Ion channel SLC30A1 410 8947 334.6634975 94.95649933 Receptor ITGB6 411 10429 334.5855495 105.0652685 Other enzyme ARF4L 412 107317 334.4278332 121.8454869 Other enzyme FASN 413 121476 333.9429392 120.8680209 Other enzyme FEN1 414 126545 333.8186808 129.5423961 Other SPDY1 415 202300 333.4461042 111.6474763 Phosphatase DUSP7 416 105208 333.3722733 105.9736161 Protease KIAA1203 417 109375 332.6248847 111.0339775 Receptor IL22RA1 418 120071 332.0526699 104.9196346 Ion channel, Other enzyme ATP8B3 419 122067 332.006738 106.5738693 Other FLJ37300 420 18224 331.923628 104.6876436 Other IQGAP2 421 2057 331.888903 113.25982 GPCR OR1A2 422 6205 331.4027826 97.29546515 Protease CASP2 423 103432 331.0905347 111.3859232 Protein kinase STK18 424 107085 331.0174791 113.5678751 Other enzyme UGDH 425 117546 330.8053804 116.4761789 Other enzyme DUOX1 426 41929 330.3190915 140.9052461 NHR NR2F6 427 112254 330.2324653 106.7015484 Other enzyme B3GNT5 428 105538 330.0716585 114.4822352 Ion channel KCNE2 429 444 329.6671336 111.1091926 Protein kinase MKNK1 430 6722 329.6243408 115.1625088 Membrane protein FLJ31819 431 40719 329.4969143 117.760941 Protein kinase, Phosphatase CAMK2G 432 115262 329.2920103 120.0833852 Other ID2 433 106223 329.2569091 143.7439467 Cytochrome P450 CYP2C8 434 120151 328.5899481 119.5213398 Ion channel SLC6A18 435 105664 328.2937206 128.417486 Protease PRSS15 436 1020 328.0148328 89.51208851 Protein kinase FLJ11159 437 112308 327.8422314 115.5164776 Extracellular Factor, Other enzyme MGAT4B 438 120484 327.5988635 115.9662965 Other enzyme SDS 439 670 327.3947747 120.0872674 Protein kinase LCK 440 1397 327.2921221 144.3640914 Protein kinase FLJ25006 441 104702 326.9211572 114.5827822 Phosphatase SYNJ1 442 1140 326.7712191 147.8017928 Protein kinase ALS2CR7 443 112418 326.2708208 124.3076331 Membrane protein, Other enzyme SIAT6 444 104693 326.0595643 123.7068081 Ion channel SCN3B 445 8943 324.9305742 108.6926675 Other enzyme IMPDH1 446 107096 324.5453144 119.1902647 Cytochrome P450 YWHAZ 447 2531 324.3124605 122.2897244 Extracellular Factor, Protease F2 448 118060 323.8821709 119.5157948 Other enzyme TRUB1 449 118590 323.302754 133.4437337 Extracellular Factor SERPINF2 450 118906 323.2258397 91.44527879 Other enzyme CA1 451 106243 321.8845718 87.98446503 Membrane protein, Cytochrome P450 CYP51A1 452 111874 320.7359898 99.33956661 Other enzyme SULT4A1 453 8193 320.6869655 116.0466428 Other enzyme PDHA1 454 2512 320.1814731 109.1446602 Receptor, Transporter, Other enzyme EBP 455 16362 319.0943973 117.9639117 Membrane protein, Protease NAALADL1 456 14218 318.5137691 104.1842766 Other enzyme SDHA 457 103493 318.4004706 107.8226635 Protein kinase MAP3K13 458 1176 317.5913147 69.8619217 Protein kinase ADCK1 459 111523 317.4037703 139.3022974 Other enzyme PCYT1B 460 33700 316.7814948 111.129705 GPCR MASS1 461 2167 316.542118 111.6354846 GPCR RDS 462 105854 316.2603175 119.0980681 Other PPP1R2 463 46281 316.2008308 110.8735838 Receptor FLJ10060 464 44894 315.4984566 117.0884463 Protease CTSC 465 38041 314.8225353 111.1933054 Other enzyme B3GNT7 466 42278 314.3075428 111.7472547 Membrane protein, Other enzyme HS3ST3B1 467 112472 314.1907068 101.1194441 Other enzyme TRNT1

TABLE 2 Target siRNA RefSeq Entrez No. ID Target symbol accession Gene ID Target description 1 113613 ANKRD3 NM_020639 54101 Homo sapiens receptor-interacting serine-threonine kinase 4 (RIPK4), mRNA. 1 105742 ANKRD3 NM_020639 54101 Homo sapiens receptor-interacting serine-threonine kinase 4 (RIPK4), mRNA. 1 105202 ANKRD3 NM_020639 54101 Homo sapiens receptor-interacting serine-threonine kinase 4 (RIPK4), mRNA. 2 117853 HLCS NM_000411 3141 Homo sapiens holocarboxylase synthetase (biotin- [proprionyl-Coenzyme A-carboxylase (ATP- hydrolysing)] ligase) (HLCS), mRNA. 2 117852 HLCS NM_000411 3141 Homo sapiens holocarboxylase synthetase (biotin- [proprionyl-Coenzyme A-carboxylase (ATP- hydrolysing)] ligase) (HLCS), mRNA. 2 117851 HLCS NM_000411 3141 Homo sapiens holocarboxylase synthetase (biotin- [proprionyl-Coenzyme A-carboxylase (ATP- hydrolysing)] ligase) (HLCS), mRNA. 3 117417 SC4MOL NM_006745 6307 Homo sapiens sterol-C4-methyl oxidase-like (SC4MOL), mRNA. 3 117416 SC4MOL NM_006745 6307 Homo sapiens sterol-C4-methyl oxidase-like (SC4MOL), mRNA. 3 117418 SC4MOL NM_006745 6307 Homo sapiens sterol-C4-methyl oxidase-like (SC4MOL), mRNA. 4 42711 CASP1 NM_033295* 834 Homo sapiens caspase 1, apoptosis-related cysteine protease (interleukin 1, beta, convertase) (CASP1), transcript variant epsilon, mRNA. 4 42626 CASP1 NM_033295* 834 Homo sapiens caspase 1, apoptosis-related cysteine protease (interleukin 1, beta, convertase) (CASP1), transcript variant epsilon, mRNA. 5 10418 CDC42 NM_001791* 998 Homo sapiens cell division cycle 42 (GTP binding protein, 25 kDa) (CDC42), transcript variant 1, mRNA. 5 10505 CDC42 NM_001791* 998 Homo sapiens cell division cycle 42 (GTP binding protein, 25 kDa) (CDC42), transcript variant 1, mRNA. 6 118135 ABCC2 NM_000392 1244 Homo sapiens ATP-binding cassette, sub-family C (CFTR/MRP), member 2 (ABCC2), mRNA. 6 116839 ABCC2 NM_000392 1244 Homo sapiens ATP-binding cassette, sub-family C (CFTR/MRP), member 2 (ABCC2), mRNA. 7 105039 CTSE NM_001910* 1510 Homo sapiens cathepsin E (CTSE), transcript variant 1, mRNA. 7 105041 CTSE NM_001910* 1510 Homo sapiens cathepsin E (CTSE), transcript variant 1, mRNA. 8 1147 FRK NM_002031 2444 Homo sapiens fyn-related kinase (FRK), mRNA. 8 1243 FRK NM_002031 2444 Homo sapiens fyn-related kinase (FRK), mRNA. 9 8225 HMBS NM_000190 3145 Homo sapiens hydroxymethylbilane synthase (HMBS), mRNA. 9 117844 HMBS NM_000190 3145 Homo sapiens hydroxymethylbilane synthase (HMBS), mRNA. 10 106087 HSD17B4 NM_000414 3295 Homo sapiens hydroxysteroid (17-beta) dehydrogenase 4 (HSD17B4), mRNA. 10 106089 HSD17B4 NM_000414 3295 Homo sapiens hydroxysteroid (17-beta) dehydrogenase 4 (HSD17B4), mRNA. 11 121011 LCN2 NM_005564 3934 Homo sapiens lipocalin 2 (oncogene 24p3) (LCN2), mRNA. 11 121012 LCN2 NM_005564 3934 Homo sapiens lipocalin 2 (oncogene 24p3) (LCN2), mRNA. 12 1766 OXTR NM_000916 5021 Homo sapiens oxytocin receptor (OXTR), mRNA. 12 1947 OXTR NM_000916 5021 Homo sapiens oxytocin receptor (OXTR), mRNA. 13 142836 PPP1R3C NM_005398 5507 Homo sapiens protein phosphatase 1, regulatory (inhibitor) subunit 3C (PPP1R3C), mRNA. 13 142834 PPP1R3C NM_005398 5507 Homo sapiens protein phosphatase 1, regulatory (inhibitor) subunit 3C (PPP1R3C), mRNA. 14 1547 MAPK9 NM_002752* 5601 Homo sapiens mitogen-activated protein kinase 9 (MAPK9), transcript variant 1, mRNA. 14 1452 MAPK9 NM_002752* 5601 Homo sapiens mitogen-activated protein kinase 9 (MAPK9), transcript variant 1, mRNA. 15 1699 MAP2K5 NM_145160* 5607 Homo sapiens mitogen-activated protein kinase kinase 5 (MAP2K5), transcript variant A, mRNA. 15 118252 MAP2K5 NM_145160* 5607 Homo sapiens mitogen-activated protein kinase kinase 5 (MAP2K5), transcript variant A, mRNA. 16 43916 TPI1 NM_000365 7167 Homo sapiens triosephosphate isomerase 1 (TPI1), mRNA. 16 43820 TPI1 NM_000365 7167 Homo sapiens triosephosphate isomerase 1 (TPI1), mRNA. 17 402 VRK1 NM_003384 7443 Homo sapiens vaccinia related kinase 1 (VRK1), mRNA. 17 401 VRK1 NM_003384 7443 Homo sapiens vaccinia related kinase 1 (VRK1), mRNA. 18 117695 SLC30A2 NM_032513 7780 Homo sapiens solute carrier family 30 (zinc transporter), member 2 (SLC30A2), mRNA. 18 117693 SLC30A2 NM_032513 7780 Homo sapiens solute carrier family 30 (zinc transporter), member 2 (SLC30A2), mRNA. 19 118261 ULK1 NM_003565 8408 Homo sapiens unc-51-like kinase 1 (C. elegans) (ULK1), mRNA. 19 118260 ULK1 NM_003565 8408 Homo sapiens unc-51-like kinase 1 (C. elegans) (ULK1), mRNA. 20 5146 GLP2R NM_004246 9340 Homo sapiens glucagon-like peptide 2 receptor (GLP2R), mRNA. 20 5237 GLP2R NM_004246 9340 Homo sapiens glucagon-like peptide 2 receptor (GLP2R), mRNA. 21 828 SNK NM_006622 10769 Homo sapiens polo-like kinase 2 (Drosophila) (PLK2), mRNA. 21 829 SNK NM_006622 10769 Homo sapiens polo-like kinase 2 (Drosophila) (PLK2), mRNA. 22 19104 SPUVE NM_007173 11098 Homo sapiens protease, serine, 23 (PRSS23), mRNA. 22 19196 SPUVE NM_007173 11098 Homo sapiens protease, serine, 23 (PRSS23), mRNA. 23 103354 PASK NM_015148 23178 Homo sapiens PAS domain containing serine/threonine kinase (PASK), mRNA. 23 978 PASK NM_015148 23178 Homo sapiens PAS domain containing serine/threonine kinase (PASK), mRNA. 24 2240 OR52A1 NM_012375 23538 Homo sapiens olfactory receptor, family 52, subfamily A, member 1 (OR52A1), mRNA. 24 2061 OR52A1 NM_012375 23538 Homo sapiens olfactory receptor, family 52, subfamily A, member 1 (OR52A1), mRNA. 25 20115 RGS17 NM_012419 26575 Homo sapiens regulator of G-protein signalling 17 (RGS17), mRNA. 25 20024 RGS17 NM_012419 26575 Homo sapiens regulator of G-protein signalling 17 (RGS17), mRNA. 26 118397 MYLIP NM_013262 29116 Homo sapiens myosin regulatory light chain interacting protein (MYLIP), mRNA. 26 118398 MYLIP NM_013262 29116 Homo sapiens myosin regulatory light chain interacting protein (MYLIP), mRNA. 27 104835 PKD1L2 NM_182740* 114780 Homo sapiens polycystic kidney disease 1-like 2 (PKD1L2), transcript variant 2, mRNA. 27 104830 PKD1L2 NM_182740* 114780 Homo sapiens polycystic kidney disease 1-like 2 (PKD1L2), transcript variant 2, mRNA. 28 119221 BPHL NM_004332 670 Homo sapiens biphenyl hydrolase-like (serine hydrolase; breast epithelial mucin-associated antigen) (BPHL), mRNA. 29 105141 USP3 NM_006537 9960 Homo sapiens ubiquitin specific protease 3 (USP3), mRNA. 30 122236 NCE2 NM_080678 140739 Homo sapiens NEDD8-conjugating enzyme (NCE2), mRNA. 31 43781 KCNK17 NM_031460 89822 Homo sapiens potassium channel, subfamily K, member 17 (KCNK17), mRNA. 32 103636 WEE1 NM_003390 7465 Homo sapiens WEE1 homolog (S. pombe) (WEE1), mRNA. 33 45922 KCNE1 NM_000219 3753 Homo sapiens potassium voltage-gated channel, Isk- related family, member 1 (KCNE1), mRNA. 34 117371 RNUT1 NM_005701 10073 Homo sapiens RNA, U transporter 1 (RNUT1), mRNA. 35 111157 M6PR NM_002355 4074 Homo sapiens mannose-6-phosphate receptor (cation dependent) (M6PR), mRNA. 36 38979 MGC39650 NM_152465 147011 Homo sapiens hypothetical protein MGC39650 (MGC39650), mRNA. 37 121933 FLJ22761 NM_025130 80201 Homo sapiens hypothetical protein FLJ22761 (FLJ22761), mRNA. 38 119829 PAPOLG NM_022894 64895 Homo sapiens poly(A) polymerase gamma (PAPOLG), mRNA. 39 19471 DNM1L NM_012062* 10059 Homo sapiens dynamin 1-like (DNM1L), transcript variant 1, mRNA. 40 120442 PSMD14 NM_005805 10213 Homo sapiens proteasome (prosome, macropain) 26S subunit, non-ATPase, 14 (PSMD14), mRNA. 41 105154 BACE NM_138973* 23621 Homo sapiens beta-site APP-cleaving enzyme 1 (BACE1), transcript variant d, mRNA. 42 6196 FKSG79 NM_032553 84636 Homo sapiens G protein-coupled receptor 174 (GPR174), mRNA. 43 105753 LCN7 NM_022164 64129 Homo sapiens lipocalin 7 (LCN7), mRNA. 44 21895 STARD8 NM_014725 9754 Homo sapiens START domain containing 8 (STARD8), mRNA. 45 120445 RASGRP2 NM_153819* 10235 Homo sapiens RAS guanyl releasing protein 2 (calcium and DAG-regulated) (RASGRP2), transcript variant 2, mRNA. 46 111807 QPCT NM_012413 25797 Homo sapiens glutaminyl-peptide cyclotransferase (glutaminyl cyclase) (QPCT), mRNA. 47 1721 ADORA1 NM_000674 134 Homo sapiens adenosine A1 receptor (ADORA1), mRNA. 48 1774 TACR1 NM_001058* 6869 Homo sapiens tachykinin receptor 1 (TACR1), transcript variant long, mRNA. 49 117712 ABCA10 NM_080282 10349 Homo sapiens ATP-binding cassette, sub-family A (ABC1), member 10 (ABCA10), mRNA. 50 1795 GPR56 NM_005682* 9289 Homo sapiens G protein-coupled receptor 56 (GPR56), transcript variant 1, mRNA. 51 117084 PRPSAP2 NM_002767 5636 Homo sapiens phosphoribosyl pyrophosphate synthetase-associated protein 2 (PRPSAP2), mRNA. 52 119926 SLC26A10 NM_133489 65012 Homo sapiens solute carrier family 26, member 10 (SLC26A10), mRNA. 53 9067 ADH7 NM_000673 131 Homo sapiens alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide (ADH7), mRNA. 54 121179 OBP2A NM_014582 29991 Homo sapiens odorant binding protein 2A (OBP2A), mRNA. 55 38327 MRGX1 NM_147199 259249 Homo sapiens G protein-coupled receptor MRGX1 (MRGX1), mRNA. 56 111813 TNFRSF13B NM_012452 23495 Homo sapiens tumor necrosis factor receptor superfamily, member 13B (TNFRSF13B), mRNA. 57 107569 TP53I3 NM_004881* 9540 Homo sapiens tumor protein p53 inducible protein 3 (TP53I3), transcript variant 1, mRNA. 58 10560 CPB2 NM_016413* 1361 Homo sapiens carboxypeptidase B2 (plasma, carboxypeptidase U) (CPB2), transcript variant 2, mRNA. 59 10235 ARFD1 NM_033228* 373 Homo sapiens tripartite motif-containing 23 (TRIM23), transcript variant gamma, mRNA. 60 104127 ADAM29 NM_021780* 11086 Homo sapiens a disintegrin and metalloproteinase domain 29 (ADAM29), transcript variant 2, mRNA. 61 112077 AGPAT3 NM_020132 56894 Homo sapiens 1-acylglycerol-3-phosphate O- acyltransferase 3 (AGPAT3), mRNA. 62 105010 CTSK NM_000396 1513 Homo sapiens cathepsin K (pycnodysostosis) (CTSK), mRNA. 63 4154 GPR39 NM_001508 2863 Homo sapiens G protein-coupled receptor 39 (GPR39), mRNA. 64 40980 TTBK NM_173500 146057 Homo sapiens tau tubulin kinase 2 (TTBK2), mRNA. 65 120756 ATP2A3 NM_174957* 489 Homo sapiens ATPase, Ca++ transporting, ubiquitous (ATP2A3), transcript variant 6, mRNA. 66 1627 FYN NM_002037* 2534 Homo sapiens FYN oncogene related to SRC, FGR, YES (FYN), transcript variant 1, mRNA. 67 122128 C20orf185 NM_182658 359710 Homo sapiens chromosome 20 open reading frame 185 (C20orf185), mRNA. 68 2207 HM74 NM_006018 8843 Homo sapiens G protein-coupled receptor 109B (GPR109B), mRNA. 69 4633 TRHR NM_003301 7201 Homo sapiens thyrotropin-releasing hormone receptor (TRHR), mRNA. 70 119952 SLC12A2 NM_001046 6558 Homo sapiens solute carrier family 12 (sodium/potassium/chloride transporters), member 2 (SLC12A2), mRNA. 71 105325 CPA3 NM_001870 1359 Homo sapiens carboxypeptidase A3 (mast cell) (CPA3), mRNA. 72 112330 D4ST1 NM_130468 113189 Homo sapiens dermatan 4 sulfotransferase 1 (D4ST1), mRNA. 73 121576 APC2 NM_005883 10297 Homo sapiens adenomatosis polyposis coli 2 (APC2), mRNA. 74 117799 MGC52019 NM_178498 159963 Homo sapiens solute carrier family 5 (sodium/glucose cotransporter), member 12 (SLC5A12), mRNA. 75 104458 VDAC2 NM_003375 7417 Homo sapiens voltage-dependent anion channel 2 (VDAC2), mRNA. 76 112453 OGT NM_181672* 8473 Homo sapiens O-linked N-acetylglucosamino (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide-N- acetylglucosaminyl transferase) (OGT), transcript variant 1, mRNA. 77 121337 CENPE NM_001813 1062 Homo sapiens centromere protein E, 312 kDa (CENPE), mRNA. 78 110844 BCR NM_021574* 613 Homo sapiens breakpoint cluster region (BCR), transcript variant 2, mRNA. 79 119422 ARHGEF1 NM_004706* 9138 Homo sapiens Rho guanine nucleotide exchange factor (GEF) 1 (ARHGEF1), transcript variant 2, mRNA. 80 119276 VCP NM_007126 7415 Homo sapiens valosin-containing protein (VCP), mRNA. 81 118817 MCCC1 NM_020166 56922 Homo sapiens methylcrotonoyl-Coenzyme A carboxylase 1 (alpha) (MCCC1), mRNA. 82 118114 FKBP7 NM_181342* 51661 Homo sapiens FK506 binding protein 7 (FKBP7), transcript variant 2, mRNA. 83 118462 KIF13B NM_015254 23303 Homo sapiens kinesin family member 13B (KIF13B), mRNA. 84 46510 TG1019 NM_148962 165140 Homo sapiens oxoeicosanoid (OXE) receptor 1 (OXER1), mRNA. 85 119129 CRMP1 NM_001313 1400 Homo sapiens collapsin response mediator protein 1 (CRMP1), mRNA. 86 119399 ELOVL3 NM_152310 83401 Homo sapiens elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 3 (ELOVL3), mRNA. 87 122166 APEX1 NM_001641* 328 Homo sapiens APEX nuclease (multifunctional DNA repair enzyme) 1 (APEX1), transcript variant 1, mRNA. 88 45063 GALR2 NM_003857 8811 Homo sapiens galanin receptor 2 (GALR2), mRNA. 89 117601 SLC12A9 NM_020246 56996 Homo sapiens solute carrier family 12 (potassium/chloride transporters), member 9 (SLC12A9), mRNA. 90 118446 KIF2C NM_006845 11004 Homo sapiens kinesin family member 2C (KIF2C), mRNA. 91 18240 FTCD NM_006657* 10841 Homo sapiens formiminotransferase cyclodeaminase (FTCD), transcript variant B, mRNA. 92 104559 CACNA2D2 NM_006030 9254 Homo sapiens calcium channel, voltage-dependent, alpha 2/delta subunit 2 (CACNA2D2), mRNA. 93 1407 MAPK14 NM_139012* 1432 Homo sapiens mitogen-activated protein kinase 14 (MAPK14), transcript variant 2, mRNA. 94 119077 HEXA NM_000520 3073 Homo sapiens hexosaminidase A (alpha polypeptide) (HEXA), mRNA. 95 1371 SPHK1 NM_021972* 8877 Homo sapiens sphingosine kinase 1 (SPHK1), mRNA. 96 106537 ATP5J NM_001003696* 522 Homo sapiens ATP synthase, H+ transporting, mitochondrial F0 complex, subunit F6 (ATP5J), nuclear gene encoding mitochondrial protein, transcript variant 3, mRNA. 97 120500 POLG2 NM_007215 11232 Homo sapiens polymerase (DNA directed), gamma 2, accessory subunit (POLG2), mRNA. 98 111654 CSF2RA NM_172245* 1438 Homo sapiens colony stimulating factor 2 receptor, alpha, low-affinity (granulocyte-macrophage) (CSF2RA), transcript variant 2, mRNA. 99 118718 SERPINB9 NM_004155 5272 Homo sapiens serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 9 (SERPINB9), mRNA. 100 120608 UBASH3A NM_001001895* 53347 Homo sapiens ubiquitin associated and SH3 domain containing, A (UBASH3A), transcript variant 2, mRNA. 101 142253 PPP1R7 NM_002712 5510 Homo sapiens protein phosphatase 1, regulatory subunit 7 (PPP1R7), mRNA. 102 111081 HIPK1 NM_198268* 204851 Homo sapiens homeodomain interacting protein kinase 1 (HIPK1), transcript variant 1, mRNA. 103 103786 GUK1 NM_000858 2987 Homo sapiens guanylate kinase 1 (GUK1), mRNA. 104 121943 C2orf8 NM_025264 80745 Homo sapiens THUMP domain containing 2 (THUMPD2), mRNA. 105 121806 ITLN1 NM_017625 55600 Homo sapiens intelectin 1 (galactofuranose binding) (ITLN1), mRNA. 106 15527 PDE1A NM_001003683* 5136 Homo sapiens phosphodiesterase 1A, calmodulin- dependent (PDE1A), transcript variant 2, mRNA. 107 143005 PKIA NM_006823* 5569 Homo sapiens protein kinase (cAMP-dependent, catalytic) inhibitor alpha (PKIA), transcript variant 1, mRNA. 108 110607 GHR NM_000163 2690 Homo sapiens growth hormone receptor (GHR), mRNA. 109 107834 AASS NM_005763 10157 Homo sapiens aminoadipate-semialdehyde synthase (AASS), mRNA. 110 121163 LOC339133 339133 111 118522 KIAA0449 23046 112 120179 UBE3A NM_130839* 7337 Homo sapiens ubiquitin protein ligase E3A (human papilloma virus E6-associated protein, Angelman syndrome) (UBE3A), transcript variant 3, mRNA. 113 34999 FLJ14681 NM_032824 84910 Homo sapiens hypothetical protein FLJ14681 (FLJ14681), mRNA. 114 6091 GPR84 NM_020370 53831 Homo sapiens G protein-coupled receptor 84 (GPR84), mRNA. 115 103829 LOC374425 374425 116 119396 ARHGEF7 NM_145735* 8874 Homo sapiens Rho guanine nucleotide exchange factor (GEF) 7 (ARHGEF7), transcript variant 2, mRNA. 117 8816 SMPD1 NM_000543 6609 Homo sapiens sphingomyelin phosphodiesterase 1, acid lysosomal (acid sphingomyelinase) (SMPD1), mRNA. 118 15339 AKAP5 NM_004857 9495 Homo sapiens A kinase (PRKA) anchor protein 5 (AKAP5), mRNA. 119 29459 FLJ21839 NM_021831 60509 Homo sapiens hypothetical protein FLJ21839 (FLJ21839), mRNA. 120 16059 PDHA2 NM_005390 5161 Homo sapiens pyruvate dehydrogenase (lipoamide) alpha 2 (PDHA2), mRNA. 121 104173 ADAM19 NM_033274* 8728 Homo sapiens a disintegrin and metalloproteinase domain 19 (meltrin beta) (ADAM19), transcript variant 2, mRNA. 122 120611 RAB25 NM_020387 57111 Homo sapiens RAB25, member RAS oncogene family (RAB25), mRNA. 123 142929 PRKAB1 NM_006253 5564 Homo sapiens protein kinase, AMP-activated, beta 1 non-catalytic subunit (PRKAB1), mRNA. 124 35220 CNP NM_033133 1267 Homo sapiens 2,3-cyclic nucleotide 3 phosphodiesterase (CNP), mRNA. 125 119469 GCHFR NM_005258 2644 Homo sapiens GTP cyclohydrolase I feedback regulator (GCHFR), mRNA. 126 121471 BCL10 NM_003921 8915 Homo sapiens B-cell CLL/lymphoma 10 (BCL10), mRNA. 127 122003 CTMP NM_053055* 117145 Homo sapiens C-terminal modulator protein (CTMP), transcript variant 1, mRNA. 128 114058 APP NM_201414* 351 Homo sapiens amyloid beta (A4) precursor protein (protease nexin-II, Alzheimer disease) (APP), transcript variant 3, mRNA. 129 117031 GLRX NM_002064 2745 Homo sapiens glutaredoxin (thioltransferase) (GLRX), mRNA. 130 110906 CXADR NM_001338 1525 Homo sapiens coxsackie virus and adenovirus receptor (CXADR), mRNA. 131 119517 PRPS1L1 NM_175886 221823 Homo sapiens phosphoribosyl pyrophosphate synthetase 1-like 1 (PRPS1L1), mRNA. 132 114048 PROS1 NM_000313 5627 Homo sapiens protein S (alpha) (PROS1), mRNA. 133 809 MERTK NM_006343 10461 Homo sapiens c-mer proto-oncogene tyrosine kinase (MERTK), mRNA. 134 137195 STX10 NM_003765 8677 Homo sapiens syntaxin 10 (STX10), mRNA. 135 118341 Dlc2 NM_080677 140735 Homo sapiens dynein light chain 2 (Dlc2), mRNA. 136 46319 KLP1 NM_020378 57106 Homo sapiens K562 cell-derived leucine-zipper-like protein 1 (KLP1), mRNA. 137 7204 KCNN4 NM_002250 3783 Homo sapiens potassium intermediate/small conductance calcium-activated channel, subfamily N, member 4 (KCNN4), mRNA. 138 119081 MAN2B1 NM_000528 4125 Homo sapiens mannosidase, alpha, class 2B, member 1 (MAN2B1), mRNA. 139 745 STK10 NM_005990 6793 Homo sapiens serine/threonine kinase 10 (STK10), mRNA. 140 119216 BCS1L NM_004328 617 Homo sapiens BCS1-like (yeast) (BCS1L), mRNA. 141 117277 SLC22A14 NM_004803 9389 Homo sapiens solute carrier family 22 (organic cation transporter), member 14 (SLC22A14), mRNA. 142 14775 NDUFA1 NM_004541 4694 Homo sapiens NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 1, 7.5 kDa (NDUFA1), nuclear gene encoding mitochondrial protein, mRNA. 143 119182 SCP2 NM_002979 6342 Homo sapiens sterol carrier protein 2 (SCP2), mRNA. 144 1286 FLJ22055 NM_024779 79837 Homo sapiens phosphatidylinositol-4-phosphate 5- kinase, type II, gamma (PIP5K2C), mRNA. 145 1961 GPR1 NM_005279 2825 Homo sapiens G protein-coupled receptor 1 (GPR1), mRNA. 146 119782 ADARB1 NM_015833* 104 Homo sapiens adenosine deaminase, RNA-specific, B1 (RED1 homolog rat) (ADARB1), transcript variant DRABA2b, mRNA. 147 135366 C20orf41 NM_032957* 51750 Homo sapiens chromosome 20 open reading frame 41 (C20orf41), transcript variant 2, mRNA. 148 42362 OPN1LW NM_020061 5956 Homo sapiens opsin 1 (cone pigments), long-wave- sensitive (color blindness, protan) (OPN1LW), mRNA. 149 12155 PVRL2 NM_002856 5819 Homo sapiens poliovirus receptor-related 2 (herpesvirus entry mediator B) (PVRL2), mRNA. 150 11 ACVRL1 NM_000020 94 Homo sapiens activin A receptor type II-like 1 (ACVRL1), mRNA. 151 7881 CAPN3 NM_212467* 825 Homo sapiens calpain 3, (p94) (CAPN3), transcript variant 9, mRNA. 152 10428 ARF4 NM_001660 378 Homo sapiens ADP-ribosylation factor 4 (ARF4), mRNA. 153 16123 HADHSC NM_005327 3033 Homo sapiens L-3-hydroxyacyl-Coenzyme A dehydrogenase, short chain (HADHSC), mRNA. 154 1049 CLK4 NM_020666 57396 Homo sapiens CDC-like kinase 4 (CLK4), mRNA. 155 919 IKBKE NM_014002 9641 Homo sapiens inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase epsilon (IKBKE), mRNA. 156 121066 PLSCR3 NM_020360 57048 Homo sapiens phospholipid scramblase 3 (PLSCR3), mRNA. 157 105169 CAPN7 NM_014296 23473 Homo sapiens calpain 3, (p94) (CAPN3), transcript variant 9, mRNA. 158 36311 RGS18 NM_130782 64407 Homo sapiens regulator of G-protein signalling 18 (RGS18), mRNA. 159 5884 GPRC5D NM_018654 55507 Homo sapiens G protein-coupled receptor, family C, group 5, member D (GPRC5D), mRNA. 160 44940 SOD3 NM_003102 6649 Homo sapiens superoxide dismutase 3, extracellular (SOD3), mRNA. 161 1398 KIS NM_144624* 127933 Homo sapiens kinase interacting with leukemia- associated gene (stathmin) (KIS), mRNA. 162 104626 SCN8A NM_014191 6334 Homo sapiens sodium channel, voltage gated, type VIII, alpha (SCN8A), mRNA. 163 15563 CCM1 NM_194456* 889 Homo sapiens cerebral cavernous malformations 1 (CCM1), transcript variant 1, mRNA. 164 136772 MAPK8IP3 NM_015133* 23162 Homo sapiens mitogen-activated protein kinase 8 interacting protein 3 (MAPK8IP3), transcript variant 1, mRNA. 165 46183 DDX19 NM_007242 11269 Homo sapiens DEAD (Asp-Glu-Ala-As) box polypeptide 19 (DDX19), mRNA. 166 5377 PPARD NM_006238* 5467 Homo sapiens peroxisome proliferative activated receptor, delta (PPARD), transcript variant 1, mRNA. 167 103491 MAP3K6 NM_004672 9064 Homo sapiens mitogen-activated protein kinase kinase kinase 6 (MAP3K6), mRNA. 168 117929 ATP5L NM_006476 10632 Homo sapiens ATP synthase, H+ transporting, mitochondrial F0 complex, subunit g (ATP5L), nuclear gene encoding mitochondrial protein, mRNA. 169 110591 CPT2 NM_000098 1376 Homo sapiens carnitine palmitoyltransferase II (CPT2), nuclear gene encoding mitochondrial protein, mRNA. 170 103534 UCK1 NM_031432 83549 Homo sapiens uridine-cytidine kinase 1 (UCK1), mRNA. 171 119066 PAFAH2 NM_000437 5051 Homo sapiens platelet-activating factor acetylhydrolase 2, 40 kDa (PAFAH2), mRNA. 172 106403 ALDH7A1 NM_001182 501 Homo sapiens aldehyde dehydrogenase 7 family, member A1 (ALDH7A1), mRNA. 173 121059 NLGN3 NM_018977 54413 Homo sapiens neuroligin 3 (NLGN3), mRNA. 174 121219 AGA NM_000027 175 Homo sapiens aspartylglucosaminidase (AGA), mRNA. 175 117366 ABCC9 NM_020297* 10060 Homo sapiens ATP-binding cassette, sub-family C (CFTR/MRP), member 9 (ABCC9), transcript variant SUR2B, mRNA. 176 105936 BCKDHB NM_183050* 594 Homo sapiens branched chain keto acid dehydrogenase E1, beta polypeptide (maple syrup urine disease) (BCKDHB), nuclear gene encoding mitochondrial protein, transcript variant 1, mRNA. 177 105919 ACYP2 NM_138448 98 Homo sapiens acylphosphatase 2, muscle type (ACYP2), mRNA. 178 103932 CRN NM_006587 10699 Homo sapiens corin, serine protease (CORIN), mRNA. 179 43139 VN1R2 NM_173856 317701 Homo sapiens vomeronasal 1 receptor 2 (VN1R2), mRNA. 180 9108 GAD2 NM_000818 2572 Homo sapiens glutamate decarboxylase 2 (pancreatic islets and brain, 65 kDa) (GAD2), mRNA. 181 111592 UST NM_005715 10090 Homo sapiens uronyl-2-sulfotransferase (UST), mRNA. 182 104388 CLCN3 NM_001829* 1182 Homo sapiens chloride channel 3 (CLCNa3), mRNA. 183 115931 SLC7A8 NM_012244* 23428 Homo sapiens solute carrier family 7 (cationic amino acid transporter, y+ system), member 8 (SLC7A8), transcript variant 1, mRNA. 184 30832 LENG4 NM_024298 79143 Homo sapiens leukocyte receptor cluster (LRC) member 4 (LENG4), mRNA. 185 105076 USP13 NM_003940 8975 Homo sapiens ubiquitin specific protease 13 (isopeptidase T-3) (USP13), mRNA. 186 44885 FABP6 NM_001445 2172 Homo sapiens fatty acid binding protein 6, ileal (gastrotropin) (FABP6), mRNA. 187 103580 MAP2K4 NM_003010 6416 Homo sapiens mitogen-activated protein kinase kinase 4 (MAP2K4), mRNA. 188 1555 EPHA5 NM_182472* 2044 Homo sapiens EphA5 (EPHA5), transcript variant 2, mRNA. 189 105163 USP25 NM_013396 29761 Homo sapiens ubiquitin specific protease 25 (USP25), mRNA. 190 105773 GGTL3 NM_052830* 2686 Homo sapiens gamma-glutamyltransferase-like 3 (GGTL3), transcript variant 1, mRNA. 191 37190 TPCN2 NM_139075 219931 Homo sapiens two pore segment channel 2 (TPCN2), mRNA. 192 121953 NIPA2 NM_030922 81614 Homo sapiens non-imprinted in Prader-Willi/Angelman syndrome 2 (NIPA2), mRNA. 193 9040 ITGAX NM_000887 3687 Homo sapiens integrin, alpha X (antigen CD11C (p150), alpha polypeptide) (ITGAX), mRNA. 194 119716 GCS1 NM_006302 7841 Homo sapiens glucosidase I (GCS1), mRNA. 195 1794 SMO NM_005631 6608 Homo sapiens smoothened homolog (Drosophila) (SMO), mRNA. 196 115136 BTNL3 NM_197975* 10917 Homo sapiens butyrophilin-like 3 (BTNL3), transcript variant 1, mRNA. 197 116921 SLC6A4 NM_001045 6532 Homo sapiens solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4), mRNA. 198 117213 ATP6V0B NM_004047 533 Homo sapiens ATPase, H+ transporting, lysosomal 21 kDa, V0 subunit c (ATP6V0B), mRNA. 199 10426 ARF1 NM_001658 375 Homo sapiens ADP-ribosylation factor 1 (ARF1), mRNA. 200 657 FER NM_005246 2241 Homo sapiens fer (fps/fes related) tyrosine kinase (phosphoprotein NCP94) (FER), mRNA. 201 46002 CST4 NM_001899 1472 Homo sapiens cystatin S (CST4), mRNA. 202 105830 PPP1CC NM_002710 5501 Homo sapiens protein phosphatase 1, catalytic subunit, gamma isoform (PPP1CC), mRNA. 203 104815 KCNK16 NM_032115 83795 Homo sapiens potassium channel, subfamily K, member 16 (KCNK16), mRNA. 204 142280 PRKAR2B NM_002736 5577 Homo sapiens protein kinase, cAMP-dependent, regulatory, type II, beta (PRKAR2B), mRNA. 205 1940 HTR2C NM_000868 3358 Homo sapiens 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C), mRNA. 206 103397 PRKCM NM_002742 5587 Homo sapiens protein kinase C, mu (PRKCM), mRNA. 207 117187 AOC3 NM_003734 8639 Homo sapiens amine oxidase, copper containing 3 (vascular adhesion protein 1) (AOC3), mRNA. 208 119405 RALGPS2 NM_018037* 55103 Homo sapiens Ral GEF with PH domain and SH3 binding motif 2 (RALGPS2), mRNA. 209 111208 PVRL1 NM_203285* 5818 Homo sapiens poliovirus receptor-related 1 (herpesvirus entry mediator C; nectin) (PVRL1), transcript variant 2, mRNA. 210 118568 SUOX NM_000456 6821 Homo sapiens sulfite oxidase (SUOX), nuclear gene encoding mitochondrial protein, mRNA. 211 383 TEC NM_003215 7006 Homo sapiens tec protein tyrosine kinase (TEC), mRNA. 212 118038 NPL NM_030769 80896 Homo sapiens N-acetylneuraminate pyruvate lyase (dihydrodipicolinate synthase) (NPL), mRNA. 213 42454 BCL2L10 NM_020396 10017 Homo sapiens BCL2-like 10 (apoptosis facilitator) (BCL2L10), mRNA. 214 118423 KIF2 NM_004520 3796 Homo sapiens kinesin heavy chain member 2 (KIF2), mRNA. 215 104231 ADAMTS6 NM_197941 345667 Homo sapiens similar to ADAMTS-10 precursor (A disintegrin and metalloproteinase with thrombospondin motifs 10) (ADAM-TS 10) (ADAM-TS10) (LOC345667), mRNA. 216 121036 OBDPF NM_017711 54857 Homo sapiens glycerophosphodiester phosphodiesterase domain containing 2 (GDPD2), mRNA. 217 5834 GPRC5B NM_016235 51704 Homo sapiens G protein-coupled receptor, family C, group 5, member B (GPRC5B), mRNA. 218 114204 GLUL NM_002065 2752 Homo sapiens glutamate-ammonia ligase (glutamine synthase) (GLUL), mRNA. 219 119258 DPYSL4 NM_006426 10570 Homo sapiens dihydropyrimidinase-like 4 (DPYSL4), mRNA. 220 111728 LILRB5 NM_006840 10990 Homo sapiens leukocyte immunoglobulin-like receptor, subfamily B (with TM and ITIM domains), member 5 (LILRB5), mRNA. 221 119072 GALNS NM_000512 2588 Homo sapiens galactosamine (N-acetyl)-6-sulfate sulfatase (Morquio syndrome, mucopolysaccharidosis type IVA) (GALNS), mRNA. 222 121053 FLJ10948 NM_018281 55268 Homo sapiens hypothetical protein FLJ10948 (FLJ10948), mRNA. 223 142803 PRKRIR NM_004705 5612 Homo sapiens protein-kinase, interferon-inducible double stranded RNA dependent inhibitor, repressor of (P58 repressor) (PRKRIR), mRNA. 224 117248 PIGL NM_004278 9487 Homo sapiens phosphatidylinositol glycan, class L (PIGL), mRNA. 225 111369 TNFRSF14 NM_003820 8764 Homo sapiens tumor necrosis factor receptor superfamily, member 14 (herpesvirus entry mediator) (TNFRSF14), mRNA. 226 118232 ATM NM_000051* 472 Homo sapiens ataxia telangiectasia mutated (includes complementation groups A, C and D) (ATM), transcript variant 1, mRNA. 227 10238 ARF3 NM_001659 377 Homo sapiens ADP-ribosylation factor 3 (ARF3), mRNA. 228 118663 SERPINB2 NM_002575 5055 Homo sapiens serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 2 (SERPINB2), mRNA. 229 13014 VAV2 NM_003371 7410 Homo sapiens vav 2 oncogene (VAV2), mRNA. 230 118922 CA14 NM_012113 23632 Homo sapiens carbonic anhydrase XIV (CA14), mRNA. 231 119792 TRAP1 NM_016292 10131 Homo sapiens TNF receptor-associated protein 1 (TRAP1), mRNA. 232 103447 CAMK1G NM_020439 57172 Homo sapiens calcium/calmodulin-dependent protein kinase IG (CAMK1G), mRNA. 233 23376 LAP3 NM_015907 51056 Homo sapiens leucine aminopeptidase 3 (LAP3), mRNA. 234 17099 MDH2 NM_005918 4191 Homo sapiens malate dehydrogenase 2, NAD (mitochondrial) (MDH2), mRNA. 235 138240 PRKCABP NM_012407 9463 Homo sapiens protein kinase C, alpha binding protein (PRKCABP), mRNA. 236 9004 CRH NM_000756 1392 Homo sapiens corticotropin releasing hormone (CRH), mRNA. 237 1785 GPR3 NM_005281 2827 Homo sapiens G protein-coupled receptor 3 (GPR3), mRNA. 238 107446 NDUFA10 NM_004544 4705 Homo sapiens NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 10, 42 kDa (NDUFA10), nuclear gene encoding mitochondrial protein, mRNA. 239 108267 C1QR1 NM_012072 22918 Homo sapiens complement component 1, q subcomponent, receptor 1 (C1QR1), mRNA. 240 122036 FLJ32389 NM_144617 126393 Homo sapiens heat shock protein, alpha-crystallin- related, B6 (HSPB6), mRNA. 241 118553 SERPINA7 NM_000354 6906 Homo sapiens serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 7 (SERPINA7), mRNA. 242 119612 DCTD NM_001921 1635 Homo sapiens dCMP deaminase (DCTD), mRNA. 243 121775 ANGPTL4 NM_139314* 51129 Homo sapiens angiopoietin-like 4 (ANGPTL4), transcript variant 1, mRNA. 244 110854 DCAMKL1 NM_004734 9201 Homo sapiens doublecortin and CaM kinase-like 1 (DCAMKL1), mRNA. 245 126062 FLJ23751 NM_152282 92370 Homo sapiens hypothetical protein FLJ23751 (FLJ23751), mRNA. 246 118792 BIA2 NM_015431 25893 Homo sapiens BIA2 (BIA2), mRNA. 247 120597 HDAC8 NM_018486 55869 Homo sapiens histone deacetylase 8 (HDAC8), mRNA. 248 119183 UPP1 NM_181597* 7378 Homo sapiens uridine phosphorylase 1 (UPP1), transcript variant 2, mRNA. 249 121277 ANG NM_001145 283 Homo sapiens angiogenin, ribonuclease, RNase A family, 5 (ANG), mRNA. 250 117497 SLC39A2 NM_014579 29986 Homo sapiens solute carrier family 39 (zinc transporter), member 2 (SLC39A2), mRNA. 251 1704 PANK1 NM_148977* 53354 Homo sapiens pantothenate kinase 1 (PANK1), transcript variant alpha, mRNA. 252 119905 SLC25A11 NM_003562 8402 Homo sapiens solute carrier family 25 (mitochondrial carrier; oxoglutarate carrier), member 11 (SLC25A11), mRNA. 253 121507 DDX21 NM_004728 9188 Homo sapiens DEAD (Asp-Glu-Ala-Asp) box polypeptide 21 (DDX21), mRNA. 254 121103 CACH-1 NM_130767 134526 Homo sapiens cytosolic acetyl-CoA hydrolase (CACH- 1), mRNA. 255 6501 ADRA1D NM_000678 146 Homo sapiens adrenergic, alpha-1D-, receptor (ADRA1D), mRNA. 256 43395 NLGN4Y NM_014893 22829 Homo sapiens neuroligin 4, Y-linked (NLGN4Y), mRNA. 257 1541 PDGFRB NM_002609 5159 Homo sapiens platelet-derived growth factor receptor, beta polypeptide (PDGFRB), mRNA. 258 648 EPHA1 NM_005232 2041 Homo sapiens EphA1 (EPHA1), mRNA. 259 22653 CENTD2 NM_139181* 116985 Homo sapiens centaurin, delta 2 (CENTD2), transcript variant 1, mRNA. 260 112041 AD-017 NM_018446* 55830 Homo sapiens glycosyltransferase AD-017 (AD-017), transcript variant 2, mRNA. 261 116939 ACLY NM_198830* 47 Homo sapiens ATP citrate lyase (ACLY), transcript variant 2, mRNA. 262 111049 FUK NM_145059 197258 Homo sapiens fucokinase (FUK), mRNA. 263 120730 RHEBL1 NM_144593 121268 Homo sapiens Ras homolog enriched in brain like 1 (RHEBL1), mRNA. 264 1776 ADCYAP1R1 NM_001118 117 Homo sapiens adenylate cyclase activating polypeptide 1 (pituitary) receptor type I (ADCYAP1R1), mRNA. 265 139134 PIP5K1B NM_003558 8395 Homo sapiens phosphatidylinositol-4-phosphate 5- kinase, type I, beta (PIP5K1B), mRNA. 266 118865 SERPINB11 NM_080475 89778 Homo sapiens serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 11 (SERPINB11), mRNA. 267 119034 GCH1 NM_000161 2643 Homo sapiens GTP cyclohydrolase 1 (dopa-responsive dystonia) (GCH1), mRNA. 268 41802 UGT2B11 NM_001073 10720 Homo sapiens UDP glycosyltransferase 2 family, polypeptide B11 (UGT2B11), mRNA. 269 115614 ATF1 NM_005171 466 Homo sapiens activating transcription factor 1 (ATF1), mRNA. 270 120142 SLC39A4 NM_017767* 55630 Homo sapiens solute carrier family 39 (zinc transporter), member 4 (SLC39A4), mRNA. 271 129420 PIK3AP1 NM_152309 118788 Homo sapiens phosphoinositide-3-kinase adaptor protein 1 (PIK3AP1), mRNA. 272 35139 LDHL NM_033195 92483 Homo sapiens lactate dehydrogenase A-like 6B (LDHAL6B), mRNA. 273 112237 AGXT2L1 NM_031279 64850 Homo sapiens alanine-glyoxylate aminotransferase 2- like 1 (AGXT2L1), mRNA. 274 118332 DNCLI1 NM_016141 51143 Homo sapiens dynein, cytoplasmic, light intermediate polypeptide 1 (DNCLI1), mRNA. 275 202390 HS3ST4 NM_006040 9951 Homo sapiens heparan sulfate (glucosamine) 3-O- sulfotransferase 4 (HS3ST4), mRNA. 276 111442 CHST2 NM_004267 9435 Homo sapiens carbohydrate (N-acetylglucosamine-6- O) sulfotransferase 2 (CHST2), mRNA. 277 119734 GNA13 NM_006572 10672 Homo sapiens guanine nucleotide binding protein (G protein), alpha 13 (GNA13), mRNA. 278 46555 MGC30208 NM_173804 255043 Homo sapiens hypothetical protein MGC30208 (MGC30208), mRNA. 279 112493 GALNT10 NM_198321* 55568 Homo sapiens UDP-N-acetyl-alpha-D- galactosamine:polypeptide N- acetylgalactosaminyltransferase 10 (GalNAc-T10) (GALNT10), transcript variant 1, mRNA. 280 120542 NEDL1 NM_015052 23072 Homo sapiens NEDD4-like ubiquitin-protein ligase 1 (NEDL1), mRNA. 281 143975 PIK3CD NM_005026 5293 Homo sapiens phosphoinositide-3-kinase, catalytic, delta polypeptide (PIK3CD), mRNA. 282 202509 KIAA0551 XM_039796 23043 PREDICTED: Homo sapiens TRAF2 and NCK interacting kinase (TNIK), mRNA. 283 26615 RHOT1 NM_018307 55288 Homo sapiens ras homolog gene family, member T1 (RHOT1), mRNA. 284 2021 MTNR1B NM_005959 4544 Homo sapiens melatonin receptor 1B (MTNR1B), mRNA. 285 1017 FLJ10074 NM_017988 55681 Homo sapiens hypothetical protein FLJ10074 (FLJ10074), mRNA. 286 44902 GAPD NM_002046 2597 Homo sapiens glyceraldehyde-3-phosphate dehydrogenase (GAPD), mRNA. 287 121821 C20orf12 NM_018152 55184 Homo sapiens chromosome 20 open reading frame 12 (C20orf12), mRNA. 288 3573 TRIM16 NM_006470 10626 Homo sapiens tripartite motif-containing 16 (TRIM16), mRNA. 289 111379 TNFRSF10C NM_003841 8794 Homo sapiens tumor necrosis factor receptor superfamily, member 10c, decoy without an intracellular domain (TNFRSF10C), mRNA. 290 119725 RPC32 NM_006467 10622 Homo sapiens polymerase (RNA) III (DNA directed) polypeptide G (32 kD) (POLR3G), mRNA. 291 119012 ARSE NM_000047 415 Homo sapiens arylsulfatase E (chondrodysplasia punctata 1) (ARSE), mRNA. 292 11202 ITGB8 NM_002214 3696 Homo sapiens integrin, beta 8 (ITGB8), mRNA. 293 119352 DPYSL5 NM_020134 56896 Homo sapiens dihydropyrimidinase-like 5 (DPYSL5), mRNA. 294 111028 MARK4 NM_031417 57787 Homo sapiens MAP/microtubule affinity-regulating kinase 4 (MARK4), mRNA. 295 6242 P2RY12 NM_022788* 64805 Homo sapiens purinergic receptor P2Y, G-protein coupled, 12 (P2RY12), transcript variant 1, mRNA. 296 6829 GPR113 NM_153835 165082 Homo sapiens G protein-coupled receptor 113 (GPR113), mRNA. 297 120986 PLIN NM_002666 5346 Homo sapiens perilipin (PLIN), mRNA. 298 282 PIK4CB NM_002651 5298 Homo sapiens phosphatidylinositol 4-kinase, catalytic, beta polypeptide (PIK4CB), mRNA. 299 119249 RAPGEF3 NM_006105 10411 Homo sapiens Rap guanine nucleotide exchange factor (GEF) 3 (RAPGEF3), mRNA. 300 121002 RBP2 NM_004164 5948 Homo sapiens retinol binding protein 2, cellular (RBP2), mRNA. 301 112098 LOC57168 NM_020437 57168 Homo sapiens similar to aspartate beta hydroxylase (ASPH) (LOC57168), mRNA. 302 120006 SLCO1B1 NM_006446 10599 Homo sapiens solute carrier organic anion transporter family, member 1B1 (SLCO1B1), mRNA. 303 9145 PLCB3 NM_000932 5331 Homo sapiens phospholipase C, beta 3 (phosphatidylinositol-specific) (PLCB3), mRNA. 304 45672 ASB10 NM_080871 136371 Homo sapiens ankyrin repeat and SOCS box- containing 10 (ASB10), mRNA. 305 5997 MC3R NM_019888 4159 Homo sapiens melanocortin 3 receptor (MC3R), mRNA. 306 5922 NR2F2 NM_021005 7026 Homo sapiens nuclear receptor subfamily 2, group F, member 2 (NR2F2), mRNA. 307 112027 LPAAT-e NM_018361 55326 Homo sapiens acid acyltransferase-epsilon (LPAAT-e), mRNA. 308 42079 KCNJ4 NM_152868* 3761 Homo sapiens potassium inwardly-rectifying channel, subfamily J, member 4 (KCNJ4), transcript variant 1, mRNA. 309 104120 ADAM18 NM_014237 8749 Homo sapiens a disintegrin and metalioproteinase domain 18 (ADAM18), mRNA. 310 104465 KCNAB2 NM_003636* 8514 Homo sapiens potassium voltage-gated channel, shaker-related subfamily, beta member 2 (KCNAB2), transcript variant 1, mRNA. 311 118241 NME3 NM_002513 4832 Homo sapiens non-metastatic cells 3, protein expressed in (NME3), mRNA. 312 12487 SMARCA3 NM_139048* 6596 Homo sapiens SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 3 (SMARCA3), transcript variant 2, mRNA. 313 139155 STX7 NM_003569 8417 Homo sapiens syntaxin 7 (STX7), mRNA. 314 7014 CLCN5 NM_000084 1184 Homo sapiens chloride channel 5 (nephrolithiasis 2, X- linked, Dent disease) (CLCN5), mRNA. 315 107742 HSD11B1 NM_181755* 3290 Homo sapiens hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1), transcript variant 2, mRNA. 316 122070 ARHGEF19 NM_153213 128272 Homo sapiens Rho guanine nucleotide exchange factor (GEF) 19 (ARHGEF19), mRNA. 317 119167 LCT NM_002299 3938 Homo sapiens lactase (LCT), mRNA. 318 121082 SFXN1 NM_022754 94081 Homo sapiens sideroflexin 1 (SFXN1), mRNA. 319 34166 CARD11 NM_032415 84433 Homo sapiens caspase recruitment domain family, member 11 (CARD11), mRNA. 320 36798 LYPLAL1 NM_138794 127018 Homo sapiens lysophospholipase-like 1 (LYPLAL1), mRNA. 321 6764 MRGX2 NM_054030 117194 Homo sapiens G protein-coupled receptor MRGX2 (MRGX2), mRNA. 322 112281 HAVCR2 NM_032782 84868 Homo sapiens hepatitis A virus cellular receptor 2 (HAVCR2), mRNA. 323 1359 DKFZp761P1010 NM_018423 55359 Homo sapiens protein kinase STYK1 (STYK1), mRNA. 324 120792 ATP6V1E1 NM_001696 529 Homo sapiens ATPase, H+ transporting, lysosomal 31 kDa, V1 subunit E isoform 1 (ATP6V1E1), mRNA. 325 120227 ATP2B1 NM_001001323* 490 Homo sapiens ATPase, Ca++ transporting, plasma membrane 1 (ATP2B1), transcript variant 1, mRNA. 326 117144 UAP1 NM_003115 6675 Homo sapiens UDP-N-acteylglucosamine pyrophosphorylase 1 (UAP1), mRNA. 327 202463 LOC375133 NM_199345 375133 Homo sapiens similar to phosphatidylinositol 4-kinase alpha (LOC375133), mRNA. 328 326 MAP2K1 NM_002755 5604 Homo sapiens mitogen-activated protein kinase kinase 1 (MAP2K1), mRNA. 329 121132 ITGA1 NM_181501 3672 Homo sapiens integrin, alpha 1 (ITGA1), mRNA. 330 40762 SNF1LK NM_173354 150094 Homo sapiens SNF1-like kinase (SNF1LK), mRNA. 331 106985 SPR NM_003124 6697 Homo sapiens sepiapterin reductase (7,8- dihydrobiopterin:NADP+ oxidoreductase) (SPR), mRNA. 332 118634 CCNF NM_001761 899 Homo sapiens cyclin F (CCNF), mRNA. 333 1709 AVPR2 NM_000054 554 Homo sapiens arginine vasopressin receptor 2 (nephrogenic diabetes insipidus) (AVPR2), mRNA. 334 119230 ARHGEF2 NM_004723 9181 Homo sapiens rho/rac guanine nucleotide exchange factor (GEF) 2 (ARHGEF2), mRNA. 335 111644 SIAT10 NM_006100 10402 Homo sapiens sialyltransferase 10 (alpha-2,3- sialyltransferase VI) (SIAT10), mRNA. 336 103331 ERBB4 NM_005235 2066 Homo sapiens v-erb-a erythroblastic leukemia viral oncogene homolog 4 (avian) (ERBB4), mRNA. 337 105105 BAP1 NM_004656 8314 Homo sapiens BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) (BAP1), mRNA. 338 6671 CD97 NM_001784* 976 Homo sapiens CD97 antigen (CD97), transcript variant 2, mRNA. 339 117749 FLJ30473 NM_144704 150209 Homo sapiens hypothetical protein FLJ30473 (FLJ30473), mRNA. 340 104678 TRPM7 NM_017672 54822 Homo sapiens transient receptor potential cation channel, subfamily M, member 7 (TRPM7), mRNA. 341 4236 P2RY1 NM_002563 5028 Homo sapiens purinergic receptor P2Y, G-protein coupled, 1 (P2RY1), mRNA. 342 119150 APOBEC1 NM_005889* 339 Homo sapiens apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1), transcript variant 2, mRNA. 343 120536 USP34 NM_014709 9736 Homo sapiens ubiquitin specific protease 34 (USP34), mRNA. 344 4084 CNR1 NM_016083* 1268 Homo sapiens cannabinoid receptor 1 (brain) (CNR1), transcript variant 1, mRNA. 345 8584 RAG1 NM_000448 5896 Homo sapiens recombination activating gene 1 (RAG1), mRNA. 346 118025 FLJ21963 NM_024560 79611 Homo sapiens FLJ21963 protein (FLJ21963), mRNA. 347 104025 MMP13 NM_002427 4322 Homo sapiens matrix metalloproteinase 13 (collagenase 3) (MMP13), mRNA. 348 142304 MAPK3 NM_002746 5595 Homo sapiens mitogen-activated protein kinase 3 (MAPK3), mRNA. 349 119004 FLJ23322 NM_024955 80020 Homo sapiens hypothetical protein FLJ23322 (FLJ23322), mRNA. 350 112199 CHST5 NM_012126* 23563 Homo sapiens carbohydrate (N-acetylglucosamine 6- O) sulfotransferase 5 (CHST5), mRNA. 351 140383 MIR16 NM_016641 51573 Homo sapiens membrane interacting protein of RGS16 (MIR16), mRNA. 352 43202 LOC134285 NM_173490 134285 Homo sapiens hypothetical protein LOC134285 (LOC134285), mRNA. 353 118558 TYR NM_000372 7299 Homo sapiens tyrosinase (oculocutaneous albinism IA) (TYR), mRNA. 354 122033 BIN1 NM_139348* 274 Homo sapiens bridging integrator 1 (BIN1), transcript variant 6, mRNA. 355 110947 GFRA3 NM_001496 2676 Homo sapiens GDNF family receptor alpha 3 (GFRA3), mRNA. 356 122374 CALML3 NM_005185 810 Homo sapiens calmodulin-like 3 (CALML3), mRNA. 357 121768 HMP19 NM_015980 51617 Homo sapiens HMP19 protein (HMP19), mRNA. 358 110667 UGT1A1 NM_000463 54658 Homo sapiens UDP glycosyltransferase 1 family, polypeptide A1 (UGT1A1), mRNA. 359 119683 SLC9A3R1 NM_004252 9368 Homo sapiens solute carrier family 9 (sodium/hydrogen exchanger), isoform 3 regulator 1 (SLC9A3R1), mRNA. 360 105368 MBTPS2 NM_015884 51360 Homo sapiens membrane-bound transcription factor protease, site 2 (MBTPS2), mRNA. 361 117476 SLC30A4 NM_013309 7782 Homo sapiens solute carrier family 30 (zinc transporter), member 4 (SLC30A4), mRNA. 362 8110 PLG NM_000301 5340 Homo sapiens plasminogen (PLG), mRNA. 363 108254 PLA2R1 NM_007366 22925 Homo sapiens phospholipase A2 receptor 1, 180 kDa (PLA2R1), mRNA. 364 119254 POLD2 NM_006230 5425 Homo sapiens polymerase (DNA directed), delta 2, regulatory subunit 50 kDa (POLD2), mRNA. 365 120528 ATP2C1 NM_001001485* 27032 Homo sapiens ATPase, Ca++ transporting, type 2C, member 1 (ATP2C1), transcript variant 3, mRNA. 366 114721 SUPT16H NM_007192 11198 Homo sapiens suppressor of Ty 16 homolog (S. cerevisiae) (SUPT16H), mRNA. 367 120404 ARHI NM_004675 9077 Homo sapiens ras homolog gene family, member I (ARHI), mRNA. 368 121560 ARPC4 NM_005718 10093 Homo sapiens actin related protein 2/3 complex, subunit 4, 20 kDa (ARPC4), mRNA. 369 8759 ORM1 NM_000607 5004 Homo sapiens orosomucoid 1 (ORM1), mRNA. 370 121689 C4.4A NM_014400 27076 Homo sapiens GPI-anchored metastasis-associated protein homolog (C4.4A), mRNA. 371 116959 CLNS1A NM_001293 1207 Homo sapiens chloride channel, nucleotide-sensitive, 1A (CLNS1A), mRNA. 372 18269 MAN1A2 NM_006699 10905 Homo sapiens mannosidase, alpha, class 1A, member 2 (MAN1A2), mRNA. 373 4118 CYP2F1 NM_000774 1572 Homo sapiens cytochrome P450, family 2, subfamily F, polypeptide 1 (CYP2F1), mRNA. 374 120313 UBE2E1 NM_003341* 7324 Homo sapiens ubiquitin-conjugating enzyme E2E 1 (UBC4/5 homolog, yeast) (UBE2E1), transcript variant 1, mRNA. 375 14778 NDUFB2 NM_004546 4708 Homo sapiens NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 2, 8 kDa (NDUFB2), nuclear gene encoding mitochondrial protein, mRNA. 376 1554 CDKL1 NM_004196 8814 Homo sapiens cyclin-dependent kinase-like 1 (CDC2- related kinase) (CDKL1), mRNA. 377 120581 RRAGB NM_016656* 10325 Homo sapiens Ras-related GTP binding B (RRAGB), transcript variant RAGBI, mRNA. 378 135789 AKAP3 NM_006422 10566 Homo sapiens A kinase (PRKA) anchor protein 3 (AKAP3), mRNA. 379 104313 GLRA1 NM_000171 2741 Homo sapiens glycine receptor, alpha 1 (startle disease/hyperekplexia, stiff man syndrome) (GLRA1), mRNA. 380 5020 PNR NM_003967 9038 Homo sapiens putative neurotransmitter receptor (PNR), mRNA. 381 103787 MAP3K11 NM_002419 4296 Homo sapiens mitogen-activated protein kinase kinase kinase 11 (MAP3K11), mRNA. 382 38222 GFRA4 NM_022139* 64096 Homo sapiens GDNF family receptor alpha 4 (GFRA4), transcript variant 1, mRNA. 383 119010 ARSB NM_000046* 411 Homo sapiens arylsulfatase B (ARSB), transcript variant 1, mRNA. 384 119464 TXNL NM_004786 9352 Homo sapiens thioredoxin-like 1 (TXNL1), mRNA. 385 111967 SH120 NM_016334 51463 Homo sapiens G protein-coupled receptor 89 (GPR89), mRNA. 386 117597 SLC6A20 NM_022405* 54716 Homo sapiens solute carrier family 6 (neurotransmitter transporter), member 20 (SLC6A20), transcript variant 2, mRNA. 387 616 PIP5K2A NM_005028 5305 Homo sapiens phosphatidylinositol-4-phosphate 5- kinase, type II, alpha (PIP5K2A), mRNA. 388 104271 PLAT NM_033011* 5327 Homo sapiens plasminogen activator, tissue (PLAT), transcript variant 3, mRNA. 389 41648 GPR38 NM_001507 2862 Homo sapiens motilin receptor (MLNR), mRNA. 390 116760 CREB5 NM_182899* 9586 Homo sapiens cAMP responsive element binding protein 5 (CREB5), mRNA. 391 103742 NEK8 NM_178170 284086 Homo sapiens NIMA (never in mitosis gene a)-related kinase 8 (NEK8), mRNA. 392 121625 FAF1 NM_131917* 11124 Homo sapiens Fas (TNFRSF6) associated factor 1 (FAF1), transcript variant 2, mRNA. 393 108793 RDH11 NM_016026 51109 Homo sapiens retinol dehydrogenase 11 (all-trans and 9-cis) (RDH11), mRNA. 394 46149 PIN4 NM_006223 5303 Homo sapiens protein (peptidyl-prolyl cis/trans isomerase) NIMA-interacting, 4 (parvulin) (PIN4), mRNA. 395 121965 BBP NM_032027 83941 Homo sapiens beta-amyloid binding protein precursor (BBP), mRNA. 396 104655 PTP4A1 NM_003463 7803 Homo sapiens protein tyrosine phosphatase type IVA, member 1 (PTP4A1), mRNA. 397 3025 VAV1 NM_005428 7409 Homo sapiens vav 1 oncogene (VAV1), mRNA. 398 23439 PLA2G3 NM_015715 50487 Homo sapiens phospholipase A2, group III (PLA2G3), mRNA. 399 31620 FLJ22655 NM_024730 79785 Homo sapiens hypothetical protein FLJ22655 (FLJ22655), mRNA. 400 4069 BAI1 NM_001702 575 Homo sapiens brain-specific angiogenesis inhibitor 1 (BAI1), mRNA. 401 107669 GFRA1 NM_145793* 2674 Homo sapiens GDNF family receptor alpha 1 (GFRA1), transcript variant 2, mRNA. 402 9248 POR NM_000941 5447 Homo sapiens P450 (cytochrome) oxidoreductase (POR), mRNA. 403 106198 ALDH3A1 NM_000691 218 Homo sapiens aldehyde dehydrogenase 3 family, memberA1 (ALDM3A1), mRNA. 404 112515 RARRES1 NM_206963* 5918 Homo sapiens retinoic acid receptor responder (tazarotene induced) 1 (RARRES1), transcript variant 1, mRNA. 405 8537 AQP1 NM_198098* 358 Homo sapiens aquaporin 1 (channel-forming integral protein, 28 kDa) (AQP1), transcript variant 1, mRNA. 406 110610 GPI NM_000175 2821 Homo sapiens glucose phosphate isomerase (GPI), mRNA. 407 43265 PPAP2C NM_177526* 8612 Homo sapiens phosphatidic acid phosphatase type 2C (PPAP2C), transcript variant 2, mRNA. 408 180 CSNK1A1 NM_001892 1452 Homo sapiens casein kinase 1, alpha 1 (CSNK1A1), mRNA. 409 117634 SLC30A1 NM_021194 7779 Homo sapiens solute carrier family 30 (zinc transporter), member 1 (SLC30A1), mRNA. 410 8947 ITGB6 NM_000888 3694 Homo sapiens integrin, beta 6 (ITGB6), mRNA. 411 10429 ARF4L NM_001661 379 Homo sapiens ADP-ribosylation factor 4-like (ARF4L), mRNA. 412 107317 FASN NM_004104 2194 Homo sapiens fatty acid synthase (FASN), mRNA. 413 121476 FEN1 NM_004111 2237 Homo sapiens flap structure-specific endonuclease 1 (FEN1), mRNA. 414 126545 SPDY1 NM_182756 245711 Homo sapiens speedy homolog 1 (Drosophila) (SPDY1), mRNA. 415 202300 DUSP7 NM_001947 1849 Homo sapiens dual specificity phosphatase 7 (DUSP7), mRNA. 416 105208 KIAA1203 NM_020718 57478 Homo sapiens ubiquitin specific protease 31 (USP31), mRNA. 417 109375 IL22RA1 NM_021258 58985 Homo sapiens interleukin 22 receptor, alpha 1 (IL22RA1), mRNA. 418 120071 ATP8B3 NM_138813 148229 Homo sapiens ATPase, Class I, type 8B, member 3 (ATP8B3), mRNA. 419 122067 FLJ37300 NM_153209 124602 Homo sapiens hypothetical protein FLJ37300 (FLJ37300), mRNA. 420 18224 IQGAP2 NM_006633 10788 Homo sapiens IQ motif containing GTPase activating protein 2 (IQGAP2), mRNA. 421 2057 OR1A2 NM_012352 26189 Homo sapiens olfactory receptor, family 1, subfamily A, member 2 (OR1A2), mRNA. 422 6205 CASP2 NM_032982* 835 Homo sapiens caspase 2, apoptosis-related cysteine protease (neural precursor cell expressed, developmentally down-regulated 2) (CASP2), transcript variant 1, mRNA. 423 103432 STK18 NM_014264 10733 Homo sapiens polo-like kinase 4 (Drosophila) (PLK4), mRNA. 424 107085 UGDH NM_003359 7358 Homo sapiens UDP-glucose dehydrogenase (UGDH), mRNA. 425 117546 DUOX1 NM_017434* 53905 Homo sapiens dual oxidase 1 (DUOX1), transcript variant 1, mRNA. 426 41929 NR2F6 NM_005234 2063 Homo sapiens nuclear receptor subfamily 2, group F, member 6 (NR2F6), mRNA. 427 112254 B3GNT5 NM_032047 84002 Homo sapiens UDP-GlcNAc:betaGal beta-1,3-N- acetylglucosaminyltransferase 5 (B3GNT5), mRNA. 428 105538 KCNE2 NM_172201 9992 Homo sapiens potassium voltage-gated channel, Isk- related family, member 2 (KCNE2), mRNA. 429 444 MKNK1 NM_003684* 8569 Homo sapiens MAP kinase interacting serine/threonine kinase 1 (MKNK1), mRNA. 430 6722 FLJ31819 NM_152529 151556 Homo sapiens G protein-coupled receptor 155 (GPR155), mRNA. 431 40719 CAMK2G NM_172170* 818 Homo sapiens calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma (CAMK2G), transcript variant 3, mRNA. 432 115262 ID2 NM_002166 3398 Homo sapiens inhibitor of DNA binding 2, dominant negative helix-loop-helix protein (ID2), mRNA. 433 106223 CYP2C8 NM_000770* 1558 Homo sapiens cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8), transcript variant Hp1-1, mRNA. 434 120151 SLC6A18 NM_182632 348932 Homo sapiens solute carrier family 6 (neurotransmitter transporter), member 18 (SLC6A18), mRNA. 435 105664 PRSS15 NM_004793 9361 Homo sapiens protease, serine, 15 (PRSS15), nuclear gene encoding mitochondrial protein, mRNA. 436 1020 FLJ11159 NM_018343 55781 Homo sapiens RIO kinase 2 (yeast) (RIOK2), mRNA. 437 112308 MGAT4B NM_014275* 11282 Homo sapiens mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase, isoenzyme B (MGAT4B), transcript variant 1, mRNA. 438 120484 SDS NM_006843 10993 Homo sapiens serine dehydratase (SDS), mRNA. 439 670 LCK NM_005356 3932 Homo sapiens lymphocyte-specific protein tyrosine kinase (LCK), mRNA. 440 1397 FLJ25006 NM_144610 124923 Homo sapiens hypothetical protein FLJ25006 (FLJ25006), mRNA. 441 104702 SYNJ1 NM_003895* 8867 Homo sapiens synaptojanin 1 (SYNJ1), transcript variant 1, mRNA. 442 1140 ALS2CR7 NM_139158 65061 Homo sapiens amyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 7 (ALS2CR7), mRNA. 443 112418 SIAT6 NM_174963* 6487 Homo sapiens sialyltransferase 6 (N- acetyllacosaminide alpha 2,3-sialyltransferase) (SIAT6), transcript variant 1, mRNA. 444 104693 SCN3B NM_018400 55800 Homo sapiens sodium channel, voltage-gated, type III, beta (SCN3B), mRNA. 445 8943 IMPDH1 NM_000883* 3614 Homo sapiens IMP (inosine monophosphate) dehydrogenase 1 (IMPDH1), transcript variant 1, mRNA. 446 107096 YWHAZ NM_003406* 7534 Homo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ), transcript variant 1, mRNA. 447 2531 F2 NM_000506 2147 Homo sapiens coagulation factor II (thrombin) (F2), mRNA. 448 118060 TRUB1 NM_139169 142940 Homo sapiens TruB pseudouridine (psi) synthase homolog 1 (E. coli) (TRUB1), mRNA. 449 118590 SERPINF2 NM_000934 5345 Homo sapiens serine (or cysteine) proteinase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 2 (SERPINF2), mRNA. 450 118906 CA1 NM_001738 759 Homo sapiens carbonic anhydrase I (CA1), mRNA. 451 106243 CYP51A1 NM_000786 1595 Homo sapiens cytochrome P450, family 51, subfamily A, polypeptide 1 (CYP51A1), mRNA. 452 111874 SULT4A1 NM_014351* 25830 Homo sapiens sulfotransferase family 4A, member 1 (SULT4A1), transcript variant 1, mRNA. 453 8193 PDHA1 NM_000284 5160 Homo sapiens pyruvate dehydrogenase (lipoamide) alpha 1 (PDHA1), mRNA. 454 2512 EBP NM_006579 10682 Homo sapiens emopamil binding protein (sterol isomerase) (EBP), mRNA. 455 16362 NAALADL1 NM_005468 10004 Homo sapiens N-acetylated alpha-linked acidic dipeptidase-like 1 (NAALADL1), mRNA. 456 14218 SDHA NM_004168 6389 Homo sapiens succinate dehydrogenase complex, subunit A, flavoprotein (Fp) (SDHA), nuclear gene encoding mitochondrial protein, mRNA. 457 103493 MAP3K13 NM_004721 9175 Homo sapiens mitogen-activated protein kinase kinase kinase 13 (MAP3K13), mRNA. 458 1176 ADCK1 NM_020421 57143 Homo sapiens aarF domain containing kinase 1 (ADCK1), mRNA. 459 111523 PCYT1B NM_004845 9468 Homo sapiens phosphate cytidylyltransferase 1, choline, beta isoform (PCYT1B), mRNA. 460 33700 MASS1 NM_000322 84059 Homo sapiens monogenic, audiogenic seizure susceptibility 1 homolog (mouse) (MASS1), mRNA. 461 2167 RDS NM_000322 5961 Homo sapiens retinal degeneration, slow (RDS), mRNA. 462 105854 PPP1R2 NM_006241 5504 Homo sapiens protein phosphatase 1, regulatory (inhibitor) subunit 2 (PPP1R2), mRNA. 463 46281 FLJ10060 NM_017986 55065 Homo sapiens G protein-coupled receptor 172B (GPR172B), mRNA. 464 44894 CTSC NM_001814* 1075 Homo sapiens cathepsin C (CTSC), transcript variant 1, mRNA. 465 38041 B3GNT7 NM_145236 93010 Homo sapiens UDP-GlcNAc:betaGal beta-1,3-N- acetylglucosaminyltransferase 7 (B3GNT7), mRNA. 466 42278 HS3ST3B1 NM_006041 9953 Homo sapiens heparan sulfate (glucosamine) 3-O- sulfotransferase 3B1 (HS3ST3B1), mRNA. 467 112472 TRNT1 NM_182916* 51095 Homo sapiens tRNA nucleotidyl transferase, CCA- adding, 1 (TRNT1), mRNA.

TABLE 3 Target No. siRNA ID siRNA sense sequence (21-mer) 1 113613 CCAAGCACGAUGUAUACAGTT 1 105742 GCGCAUGGAGCUUUUGGAATT 1 105202 GGAGAAUAUCGUGCGCAUCTT 2 117853 CGAAAGUUAACAAAACUCCTT 2 117852 GGACGGUAUGGAGCAUGUUTT 2 117851 GCCUGAACCUUCUCUUGAGTT 3 117417 CGUAAACCUUCCUGAAAGATT 3 117416 CCAUUCGUUUAUUAGAAACTT 3 117418 CCUUUAAUUACCUUCCUAGTT 4  42711 GAAUAUGCCUGUUCCUGUGTT 4  42626 GACUCAUUGAACAUAUGCATT 5  10418 GGAUUAUGACAGAUUACGATT 5  10505 GGCUGUCAAGUAUGUGGAGTT 6 118135 GCAGACAAUGGUGUGUACATT 6 116839 GCAGGUAUUCGUUGGUUUUTT 7 105039 GGCCCAUAUAUUGCAUUUATT 7 105041 GGAGGCAGAUAAUGCUGGUTT 8   1147 GGCAGACAAGUCAACCGUGTT 8   1243 GGCAUGGCCACUACUUUGUTT 9   8225 GGAAUGCAUGUAUGCUGUGTT 9 117844 CCAAUCCUACUAAUAAACCTT 10 106087 GGAAUAUAUGGCAACUUUGTT 10 106089 GGGCACACUACACUAUUAATT 11 121011 CGAGUUACCUCGUCCGAGUTT 11 121012 GCAUGCUAUGGUGUUCUUCTT 12   1766 GGUGCACAUCUUCUCUCUGTT 12   1947 GGUACCUAUCAGUUUGUAUTT 13 142836 CCGAUUACUUAAGUUUCCGTT 13 142834 CGACGACAUUUUGUGAAUATT 14   1547 GGUUAUUCACAUGGAGCUGTT 14   1452 GGGAUUGUUUGUGCUGCAUTT 15   1699 GGUUAAGCUGUGUGAUUUUTT 15 118252 GCCCUCCAAUAUGCUAGUATT 16  43916 GAGAAGGCAUGUCUUUGGGTT 16  43820 GAGAGAAGGCAUGUCUUUGTT 17    402 GGAGGCUUUGGCUGUAUAUTT 17    401 GGAAUGGAAAGUAGGAUUATT 18 117695 CCAUCCUGAGAGAUGUGAUTT 18 117693 GCCAGAAUACAAGUAUGUATT 19 118261 CCCAAGCACUUUAUGCAUATT 19 118260 GCGAAUUUUGUGUGAUUUCTT 20   5146 GGCAUGUCUGAGAGACUUATT 20   5237 GGAACCUUCUGGCAUAUUUTT 21    828 GGUAUACAAUGCCGUCCUCTT 21    829 GGACUUUGGAACUGUGAAUTT 22  19104 GGCCAAGCAAUAUCUGUCUTT 22  19196 GGGUCUUCAGGAAAGUCUCTT 23 103354 GGACCAGCAAAUCACUGCCTT 23    978 GGUCUGAACCAGUGGAUGUTT 24   2240 GGAUUUGACCUCACAUUCATT 24   2061 GGGUAUAGAGUCAGGCAUCTT 25  20115 GGUUUUCCAUGGUUAAGUUTT 25  20024 GGAAGUCUUGUCCUGGUCUTT 26 118397 GGAGCAGACUAGGCAUAUCTT 26 118398 GCAGACUAGGCAUAUCUUUTT 27 104835 GGCGAUAUGGAGGUGUACATT 27 104830 GGAGGCCAUUUGGUCUUCATT 28 119221 CGGUUUCAUGCCGACUUCATT 29 105141 GGCAGCCAGACUGCAUUUATT 30 122236 GUUGUCUGCUUACCUUAACTT 31  43781 GCUCUAAGGAAGACUUCAATT 32 103636 GGCUGGAUGGAUGCAUUUATT 33  45922 GCUACAUCCGCUCCAAGAATT 34 117371 CCAUUCUAGAUUGCAUUUATT 35 111157 GCGUGGCAAAGUCCAAGAUTT 36  38979 GGUGAUCAAGAAGGUAAAGTT 37 121933 GGAAUCAUUGCAUGCUUAATT 38 119829 GCCUUGAUAUAAGGUGUAUTT 39  19471 GGAAAUAAUAAGGGAGUAATT 40 120442 GGCAUUAAUUCAUGGACUATT 41 105154 GGCAGUCUCUGGUAUACACTT 42   6196 GGUCUCAUAGGGAAUAUAUTT 43 105753 GUGGCAGUGUGACCAAGAATT 44  21895 GGAAAGUAAGUGCUGGUCUTT 45 120445 GGCUCUGCUAGACCAAGAATT 46 111807 GGUGGUUCGAAAGACUUCATT 47   1721 GGUCAUCAGCAUGGAGUACTT 48   1774 GGACAGUGACGAACUAUUUTT 49 117712 GCGAGUUUUACCUGAUAAATT 50   1795 GGGAAGACUUUCGCUUCUGTT 51 117084 GCUCCUGAUCAUGGUGUAUTT 52 119926 GGAGAAAAGGAGACUUCAATT 53   9067 GGCUAUUUGCCAGCAUAUATT 54 121179 CGGACGACUACGUCUUUUATT 55  38327 GGGAAGUCUUAUUUUGUCATT 56 111813 CCCUAAGCAAUGUGCAUACTT 57 107569 GGUCUAGGGACAAUAAGUATT 58  10560 GGCAUCCUGAUAUGCUUACTT 59  10235 GGUGCUAGAGUGUGGAGUUTT 60 104127 GGACAAAGUGUUUGCUUGATT 61 112077 CGGAGUGUACACUGUUCACTT 62 105010 GGAAGAGAGUUGUAUGUACTT 63   4154 GGCUGAUUGUUGUGACAUUTT 64  40980 GGAAAGACCAUGUUUGUAGTT 65 120756 CCUGGUGGUUUGUGUAUGATT 66   1627 GGAAGUUUACUGGAUUUCUTT 67 122128 CCAAAGUGGGCAUGCAUUGTT 68   2207 GGCAUGAUUAAACAAGGCATT 69   4633 GGUACAUAGCAAUCUGUCATT 70 119952 CCGUGGUGGAGUUGCUUAATT 71 105325 GAAAAAAUCGUUCCAAGAATT 72 112330 GGAUGUGCUGCCUAAGUAUTT 73 121576 CGUGUAAAUAGUGGUAAAUTT 74 117799 CGAUUCUCUACACAGGAGUTT 75 104458 GGAUCAAUUUAUCAGAAAGTT 76 112453 GCAUUAUCGACAUGCAUUGTT 77 121337 CCAAUCAUCGAUUCUGCCATT 78 110844 GGAUCCAACGACCAAGAACTT 79 119422 CCGAUCACAAAGCCUUCUATT 60 119276 GGUAUACCUUAAGCCGUACTT 81 118817 GCCAAAAAACUGGGUGUACTT 82 118114 CGAUGAACUAUAGCAUAUUTT 83 118462 GCCGAAGGUGUUUGCUUAUTT 84  46510 GACUCCAGAACCUUCUCUCTT 85 119129 CGAUGACCAAUCCCUUUAUTT 66 119399 GCAAGGUCAUAGAACUCGGTT 87 122166 GAAAGGAUUAGAUUGGGUATT 88  45063 GCAUCCUGACGGUUGAUGUTT 89 117601 GCUUCACUUGUGACAGGACTT 90 118446 GCAACUUGUUUUGCAUAUGTT 91  18240 GGAAGUUCCUCAUUGCUUUTT 92 104559 GGAGUCCUAUGACUAUCAGTT 93   1407 GGUGGAUGUAUAGCAUUUUTT 94 119077 GGAGAUGAGGUUGAUUUCATT 95   1371 GGGCAGGCAUAUGGAGUAUTT 96 106537 GGACCUGUUGAUGCUAGUUTT 97 120500 GCAGAUACGAAAUGGUGUUTT 98 111654 CGAAUGUUCGUGCACAUUUTT 99 118718 CCCUUAAAGCUCACUUCAATT 100 120608 GCACGAGACGCACUUUUAUTT 101 142253 GGAGCUACAGAGUCUUCGATT 102 111081 GGCAGACCGAAGAGAAUACTT 103 103786 GAACGGCAAAGAUUACUACTT 104 121943 CCAUUGUAUUGUUGCUUAGTT 105 121806 CGAAUGUCCUAGUGCAUUUTT 106  15527 GGAAUACUAAGAUGCUUGGTT 107 143005 GCACUGUUUUUAGCAUUACTT 108 110607 CCUGAGCGAGAGACUUUUUTT 109 107834 GGGUCUAUAGAGUUUAUGATT 110 121163 GGUGCAAUGCGACUAUCACTT 111 118522 CCUAUGACUUUGUCUUCGATT 112 120179 CGAAUGAGUUUUGUGCUUGTT 113  34999 GGUUCUAUAGUCCUUUUAATT 114   6091 GGUAAUAGGAGAAUAGGUGTT 115 103829 GGAAAUGACUACAGAGCUGTT 116 119396 CGUACCUACGGCCAUUGCATT 117   8816 GGAGACAAAGUGCAUAUAATT 118  15339 GGAAAAGGCAUCCAUGCUUTT 119  29459 GGCAAGAGGAUAUUCUUCUTT 120  16059 GGAUGAUGCUGACUGUUCGTT 121 104173 GGUGGUGGAAUGUGUCUCUTT 122 120611 GGUCUUCAUGCCCUAUCACTT 123 142929 CCUACAUUCUCGAUUUUUCTT 124  35220 GGCCUUCAAGAAGGAGCUGTT 125 119469 GCCUUGGGAAACAACUUUUTT 126 121471 GCAUACUUCUAGGAUAGCUTT 127 122003 GGAAGUCAUUCUUAAGGACTT 128 114058 GGCAGUUAUCCAGCAUUUCTT 129 117031 GCAUAGUUGGUCUUGGUGUTT 130 110906 GCAUCUAUCAGAUUAAGUUTT 131 119517 CGACAGUCUAAUGGAGCUUTT 132 114048 CCAAACAGGGUAAUCUUGATT 133    809 GGGAAGAAGCCAAGCCUUATT 134 137195 CCAUCGGUAUAGUGGAAGCTT 135 118341 CGAGACAAAGCACUUCAUCTT 136  46319 GCAAAGACCUGUGAAGCUATT 137   7204 GGAACUGGCAUUGGACUCATT 138 119081 CCGUGGACCAGUACUUUUATT 139    745 GGUUUACAAGGCCAAGAAUTT 140 119216 GCUAUGCCUGGUUGCUUAGTT 141 117277 GCAUCAUGUCGGCCUUCUUTT 142  14775 GGGUUGCUCAUUUUGGGUATT 143 119182 CCUCCUGAUCAAUAAGUAUTT 144   1286 GGUCAACAAUCACCUUUUCTT 145   1961 GGAACUCAGAAACCAAGAATT 146 119782 GGACUCAAGUAUGACUUCCTT 147 135366 CCAAGGUCCUGGAAUGUCUTT 148  42362 GCAUUGUGAACCAGGUCUCTT 149  12155 GGAUGUGCGAGUUCAAGUGTT 150     11 GGAGCACCUGAUUCCUUUCTT 151   7881 GGAACAGCAACAAUUCCGGTT 152  10428 GGAUUUGGCAAAUGCUAUGTT 153  16123 GGGAAUUGAGGAAAGCCUUTT 154   1049 GGAAAAGAUCCAGGAGUAUTT 155    919 GGUACUGGUGAUGGAGUACTT 156 121066 CCAAAGACGGUGGAUAUAGTT 157 105169 GGAAAUCUAGUGGUGACUATT 158  36311 GGCUUUUACCAGAUUUCUUTT 159   5884 GGUAUGAUGUUUGUGAAUATT 160  44940 GUGGAUCCGAGACAUGUACTT 161   1398 GGCAAUCAGGAUGUAAAGUTT 162 104626 GGAAAGACGUAACAGGAGATT 163  15563 GGAACGACAGUGGGUAGAUTT 164 136772 CCCACAUAUCUGCUCUGUATT 165  46183 GAUACCAAUGGUGCUGUUGTT 166   5377 GGCCUUCUCCAAGCACAUCTT 167 103491 GGUGGGUAUGUACAAGGUCTT 168 117929 GGUCACAAUUUCUCUUGAUTT 169 110591 CCUCAUUAUCGCCAAGGAUTT 170 103534 GGACAGUACAAUUUUGACCTT 171 119066 GCGAGUGUUUACGGGUGUUTT 172 106403 GGUCUACUUGUACUAUCAATT 173 121059 GCGAGAAUAUUGCCUUCUUTT 174 121219 GCAUGAUCAGUCCUGAUUGTT 175 117366 CCUUUGCACUAUAUACAUCTT 176 105936 GGCCAAAGGACUUCUUUUGTT 177 105919 GCCCUAGUUCUCGCAUUGATT 178 103932 GGAAGCAUCCAUCAGCUGGTT 179  43139 GUCUCCUGCUUUGUAUCCATT 180   9108 GGCACAGGUGUAAAUAUAGTT 181 111592 GGUUAUUUUACAUCAUUCCTT 182 104388 GGAUGGCUAGUAGUAACACTT 183 115931 GCCCAAGUGUUUCAGUGACTT 184  30832 GGCGGCUUCCUUGGAGUAUTT 185 105076 GGAUGAACUGAUCGCUUAUTT 186  44885 GUUCACUGUUGGCAAGGAATT 187 103580 GGAGCUUAUGGUUcUGUCATT 188   1555 GGUCAGAGAUGUAGGACCUTT 189 105163 GGUAAUCAUGUUACUAACCTT 190 105773 GCAGCCUUGUGUUUGGGUATT 191  37190 GGUGUUUCUGGAUGCAUAUTT 192 121953 GCUCUCAGCGUGCUAGUAATT 193   9040 GGACAUUGUGUUCCUGAUCTT 194 119716 GGAAAUCAAGCCCUGCCAATT 195   1794 GGUGCAGAACAUCAAGUUCTT 196 115136 CCCUAUAUCCAGCAUGCGATT 197 116921 CCGAAAUGGAUGCAUUUCATT 198 117213 GCUGUGUCCCUUAGCCUUUTT 199  10426 GGGUCCGAUUUGCCAUCGATT 200    657 GGCUCACCAUGAUGAUUAATT 201  46002 GCUCCAAGGAGGAGAAUAGTT 202 105830 GCCUAUCCUACUAGAACUUTT 203 104815 GGCUCCUCUUACCUCCCAATT 204 142280 GCUUUAUUGAGUCACUGCCTT 205   1940 GGUGAUGAAUUUACCAUCATT 208 103397 GGGUGUGGUCUGAAUUACCTT 207 117187 GCAGCUCAAGUUAGCAUUUTT 208 119405 CCAGAUGAGCUUUCAAGUUTT 209 111208 CCAAUUGGAUAGAGGGUACTT 210 118568 CCAUCAAGGGCUAUGCAUGTT 211    383 GGUUGUUCAUGAUGCUAACTT 212 118038 CCAAAGAUAUCGUGAUUAATT 213  42454 GGCUUUUCUGUCAUGCUUGTT 214 118423 CCUGGAGAGCAUCUUUUCATT 215 104231 GGAGGUGGUCUGUAAAAGGTT 216 121036 CCAGCAAGUGCGACUGUAUTT 217   5834 GGAAAUUUGGAAAUCCUAGTT 218 114204 CCCUAACAAGCUGGUGUUATT 219 119258 CCUAAGCUUCCAUGUAGCCTT 220 111728 GGAAAAACCCUCAGGUGUGTT 221 119072 GCAAGAUUGUCGGCAAGUGTT 222 121053 CGAGGGUUGGGUUUGCUUUTT 223 142803 CCUUUGACUAAUAGGAGUUTT 224 117248 GCAAUCACAUUGCUCUGUATT 225 111369 CCACUGACCCACAGACUCUTT 226 118232 GCACUGACCUCUGUGACUUTT 227  10238 GGAAAGACCACCAUCCUAUTT 228 118663 GCUUCCGGGAAGAAUAUAUTT 229  13014 GGAACAGCGAGCUGUUUGATT 230 118922 GGCAUAAAUUCCUUCUCAGTT 231 119792 GGCCGAGACAAAGAAGCUUTT 232 103447 GGUCUUGUCGGCAGUGAAATT 233  23376 GGGAAGACUCGAACCUUUUTT 234  17099 GGUUGUGAUGUGGUAGUUATT 235 138240 CCUCCUACGGGCCUUUUAUTT 236   9004 GGUGUUUAUAGUGGUGUUUTT 237   1785 GGAUGUGCAGAAAGUGCUGTT 238 107446 GGACAAUCGCACUUUAUACTT 239 108267 GGUAUUUUCUACGGGUGUUTT 240 122036 CCAAACUGUACAGACUCUCTT 241 118553 GCCAAGCAGGAGAUUAACATT 242 119612 CCGAUGUGAAAGGCUGUAGTT 243 121775 CGAAAGACGGUGACUCUUGTT 244 110854 GGAAUGUGUAGAAAGAUCGTT 245 126062 CCAGUUUUAGAUGACUCUUTT 246 118792 CCUUGGAUUACAUAAGGAUTT 247 120597 CGGGCCAGUAUGGUGCAUUTT 248 119183 CCGCAUGGGAGAUGUUCUTT 249 121277 GGGCCCAAAGAAAGAGCUATT 250 117497 GCAGGGUUCAUGCAUAUGATT 251   1704 GGUGUCAGAUAGUAAUAUCTT 252 119905 GCAGUUCUUACUGGACUCATT 253 121507 GCAUCUGGCUAUUAAGUGCTT 254 121103 GGUCAACUUUCAAUUACUGTT 255   6501 GGUGCCCAGAACUCUUUUCTT 256  43395 CAACAACAACUACAAGGAGTT 257   1541 GGACAGAAGCUACAUCUGCTT 258    648 GGAGACCUUCAACCUUCUGTT 259  22653 GGGAUCUUACAUCUAUCAGTT 260 112041 CGACAGAAUAUAACUAACCTT 261 116939 GGAGUUCUAUGUCUGCAUCTT 262 111049 GGCAUUCCCUAUGGCUUAGTT 263 120730 GGACUUCACGGGUAUGGUUTT 264   1776 GGAUUAUUACUACCUGUCATT 265 139134 CCUCUAAUAGAACUGUCUATT 266 118865 GCAAUAUUUAAGCUGUUCUTT 267 119034 GCAACACACAUGUGUAUGGTT 268  41802 GAUAGAUAGGACAACUUCATT 269 115614 GCCUUACAGUUGGCAAGUCTT 270 120142 CGUGAUGGCUGCAUAUGGATT 271 129420 GGUUAUAGUGUGAGACUUGTT 272  35139 GGGAGAAACGCGCCUUAAUTT 273 112237 GCCAACGACUUAGCCUUACTT 274 118332 GCACUUAUUUACACUUCAGTT 275 202390 CCAGGAAUUGUUCUAGUAATT 276 111442 GCCUUUCGUGGUAUCUGCATT 277 119734 GCAACGUGAUCAAAGGUAUTT 278  46555 GCUCCUCAUCACACUGUCATT 279 112493 GCCUUUACUCUGAGGAUAATT 280 120542 CCCAACCAUAAUGGUAAAATT 281 143975 CGACUUUCGCGCCAAGAUGTT 282 202509 CCGGAAUAUUGCUACAUACTT 283  26615 GGCUAAUGUCAUCUGUAUATT 284   2021 GGUAAUUUGUUCUUGGUGATT 285   1017 GGAAGUUCGUGAACAUGUATT 286  44902 GGCUGAGAACGGGAAGCUUTT 287 121821 GCACGGAGAUAAUGAGAAUTT 288   3573 GGUACUAUUUUGAGGUGGATT 289 111379 CGGGAUUUAUUCAGCCUUGTT 290 119725 GGCAACCUAUUAGGCAUGATT 291 119012 GGCUAUGCCACUGGACUCATT 292  11202 GGAUUUCAUUUCAGGUGGATT 293 119352 GGACCUGUACAUGCUUCGATT 294 111028 GGUCACAAGUUGCCAUCUATT 295   6242 GGACCACUGAGAACUUUUGTT 296   6829 GGUGAGUACAUGAGCUGCUTT 297 120986 CCCUAGUCUUCGAAAUGUUTT 298    282 GGCCUGCCAGGAGGUGUUGTT 299 119249 GGAACCGGUAUACAGUGAUTT 300 121002 GGCAUCUGGGUGGGUUUUATT 301 112098 GCGCAUUCCUUUGAUUGGUTT 302 120006 GGAGCUAGAUUCAUAUCCUTT 303   9145 GGUCUGGUCUGAGGAGCUATT 304  45672 GCUGGCAGAUCUGCUUCUATT 305   5997 GGUACGUCACCAUCUUUUATT 306   5922 GGCCAUAGUCCUGUUCACCTT 307 112027 GGGUUAAAAUGGCUGCCAUTT 308  42079 GGUGGACUACUCACGUUUUTT 309 104120 GGGAAAGGGAUAUGUAAUATT 310 104465 GGCACUGGUUAGGAAGGAUTT 311 118241 GGUUGGCAAGAACCUGAUUTT 312  12487 GGUCAUGUGGUUGGACUACTT 313 139155 GCUAUUGUAUAAAGGAUGGTT 314   7014 GGGAGCCUUUGCCUACAUATT 315 107742 GGGAUUUUGGGACUGUUCUTT 316 122070 GCUAGGGAAGUUUGCCGUUTT 317 119167 CCUAUGACUUUUUUGGGUUTT 318 121082 CGAGCCAAUCAUUUCUUCATT 319  34166 GGAUGAAGAUGAAGUGCUUTT 320  36798 GGUGAUUCUGGACAAGGAUTT 321   6764 GGACAUUGCUGAGGUGGAUTT 322 112281 GGUGAAAGCAUAACUUUUUTT 323   1359 GGGCUAGAAAAGAAUGUAATT 324 120792 GAGCAAGAGAUGACCUUAUTT 325 120227 GCCAUAGUAUCAUUGGGCCTT 326 117144 CGAUAGGAAUAGCUUUUAUTT 327 202463 GCUCUGACCAAGUGGAGAUTT 328    326 GGAGCUAGAGCUUGAUGAGTT 329 121132 GCUAUAACCGAGGAAAUUUTT 330  40762 GGAAAACUGUGAACUUUCUTT 331 106985 GGUUAUGGGUAUUGGUGUCTT 332 118634 GCGCAGCUGUCUUUAGCCATT 333   1709 GGACACUUCAUCGUGAGGATT 334 119230 GGUAAUCUACAGUGAGCUGTT 335 111644 GGACAACCUUCCGACUUUUTT 336 103331 GGAUCGAUAUGCCUUGGCATT 337 105105 GGCCCAUAAUAGCCAUGCCTT 338   6671 GGUCACCAUCCAGAAUGUCTT 339 117749 GCUCACAUGCAGUAGACUUTT 340 104678 GGUACUAAUGCAUCUGCAUTT 341   4236 GGUUCAUCUUUCAUGUGAATT 342 119150 CCUUGUUAACAGUGGAGUATT 343 120536 GCCUAGAUCUUGCAUUUAATT 344   4084 GGCCUUCCUACCACUUCAUTT 345   8584 GGAGAAAAAGAUGUCUUUUTT 346 118025 GGAAGCAUUCAAGCAUUUATT 347 104025 GGUUGAUGCGGAGGUGUUUTT 348 142304 CCGGAUGUUAACCUUUAACTT 349 119004 GCCAUCUUAGCAACUUUCUTT 350 112199 GCAGGUCCCUACUAUCAACTT 351 140383 CCUCACUUCUAGACUUUCATT 352  43202 GCAUUGGGAUAUUAAGUAGTT 353 118558 CCUUUACGGCGUAAUCCUGTT 354 122033 CGGUCUGUGUGCUGUUUGATT 355 110947 GCCUAUGGUAGCUGGACUUTT 356 122374 GAAGCAGAGCUGACCUUAGTT 357 121768 CCCAUAGUGAAAUGUGCUGTT 358 110667 GGAUGUGAAAGAGUCUUUUTT 359 119683 GCAAGAAAAACGAACUCUUTT 360 105368 GCAUUUGUUGAUCUGUUCATT 361 117476 GCUGUGCAAAGAACUAUCCTT 362   8110 GGAAGUAUAGAAGAAUGUGTT 363 108254 GGUACGCUGUUAAGUAUUATT 364 119254 CGUGUCAAAGCUGGUUACGTT 365 120528 CCAGAGAUUUGUUUUAUGATT 366 114721 GGAAUUAAGACAUGGUGUGTT 367 120404 GCCAAGACCGAUGUGAAUGTT 368 121560 GCUCCUGUUACAACCUGUGTT 369   8759 GGGACACCAAGACCUACAUTT 370 121689 GCGAUCAUGUCUACAAGGGTT 371 116959 CCUCUUAGGUUGUAUCCUUTT 372  18269 GGGCUACCUUGAGACUUUCTT 373   4118 GGCAGAUGUGGCAUGUCUUTT 374 120313 GGGUGGGAGUUGGUAAAGATT 375  14778 GGUGAGAAUUUCAAGGAUUTT 376   1554 GGAAAAUCGGAUGUGGAUCTT 377 120581 CCCUCUAUAAGGCUUGGUCTT 378 135789 GCCUCAGUAAGAUAGCAUCTT 379 104313 GGUAGCAGAUGGACUAACUTT 380   5020 GGCACUGAAACUCACACUGTT 381 103787 GGCUUUGGCAAGGUGUACATT 382  38222 GGCAUCUUGGUUGUAAGUCTT 383 119010 GGGCUAUAGCCCUCAUAACTT 384 119464 GCUGCCACCAACAAUAUAUTT 385 111967 GCAAUAUCCGACUACUGCATT 386 117597 CCAACACUUUUGACCUUCATT 387    616 GGUGGACAAUCACCUUUUUTT 388 104271 GGAAAGACGGAUUGCAUUATT 389  41648 GUACUUUAACAUCGUCGCUTT 390 116760 CCUUUUCUGUAUAUAGCCATT 391 103742 GGAGCCUCUGCUGAGUAUATT 392 121625 GCUAUCAAUGGUGUAAUACTT 393 108793 GGAGCUCGAGUAUAUUUAGTT 394  46149 GAAAAGAUAUUGGAUGCUCTT 395 121965 GCCUAAUUGAUUUCAUUCUTT 396 104655 GGAAAUGCAGCCUAGUCUUTT 397   3025 GGAAGAUUAUUCUGAAUACTT 398  23439 GGUUGAUGUAACCUUUUAATT 399  31620 GGUGGAAAUGAUGUUUAUCTT 400   4069 GGACAACUUUGGUGCUGUGTT 401 107669 GGCUUUGGGAUAUGCUGUATT 402   9248 GGAGUCCAACAAGAAGCACTT 403 106198 GGAUCUGUACCCAGUAAUCTT 404 112515 CCAUCAAUGUAACUUGUACTT 405   8537 GGAAAAUGACUUGUAAGGUTT 406 110610 CCAACCAUGGGCAUAUCCUTT 407  43265 GACCUGGCCAAGUACAUGATT 408    180 GGAAGUGGCAGUGAAGCUATT 409 117634 CCUAUCCAUUACUUAAGGATT 410   8947 GGUGCAGAAACCUGUGAAGTT 411  10429 GGACUGUGGAGACGUAAAUTT 412 107317 GGUAUGCGACGGGAAAGUATT 413 121476 GCUACUUUGGCCGUAAGGUTT 414 126545 GGAGGUUAUGGCCAUUGCATT 415 202300 GUUCACCUACAAGGAGAUCTT 416 105208 GGCAAAUGUUCUCACUGCATT 417 109375 GGAGUUUCAGACCCUAUCCTT 418 120071 GGGAUAUGCAAACCUCAUCTT 419 122067 GGACUCAGACACAGGUGAUTT 420  18224 GGCGGCAGAACAUUGCUUATT 421   2057 GGCAGACAGCUAUACCUUGTT 422   6205 GGACAUCAUCACCUUGGAATT 423 103432 GGGAUGUUGUAUCUUCAUUTT 424 107085 GGUAGCAACAGCGAUUGGATT 425 117546 GCUAUGCAGAUGGCGUGUATT 426  41929 GCAUUACGGUGUCUUCACCTT 427 112254 CCAAUCGAUAAUCACAUUGTT 428 105538 GACGGGAACACUCCAAUGATT 429    444 GGAAAGCAAUCACUUCUCATT 430   6722 GGCUUUUUCCAGCCUUACUTT 431  40719 GGAGAUCAUUAAGAUUACATT 432 115262 GCGGUGUUCAUGAUUUCUUTT 433 106223 GGACAUUCCCACUAUUAUGTT 434 120151 GGGAAGGUGAUUUACUUCATT 435 105664 GAGAUGACAGCAAUGAGUCTT 436   1020 GGACAACAAUUUGCAUUAATT 437 112308 CGUAAGUCCACAUAUACUUTT 436 120484 GGCUAUGAAUUGGACCUUUTT 439    670 GGAGUUCAAUAAAUGUCUGTT 440   1397 GGGAAAACGGCACCUUUUCTT 441 104702 GGCAAUCAAGGGUACAUACTT 442   1140 GGAUCUGAGGCAGGGUUUUTT 443 112418 CCAAGUACGCAAACUUUUCTT 444 104693 GGAGUGAUUAGUUCGGGUUTT 445   8943 GGAUUCAUAGACUUCAUAGTT 446 107096 GGAAAAAUGAAUUGCUUGGTT 447   2531 GGUAACUGUGCUGAGGGUCTT 448 118060 GGGUCCAAGAGAUAUACUGTT 449 118590 GCUCCUUAAGGCUCUUUUGTT 450 118906 CCUAUUAGUGUCUCCUACATT 451 106243 GGUCACAUUUAUGUGGAAGTT 452 111874 CGUGCUUUUUCUCAAGUAUTT 453   8193 GGAUGGGCUCAAAUACUACTT 454   2512 GGAAAUAAAAGAUCUUGACTT 455  16362 GGCUCCUACUACGAGUAUUTT 456  14218 GGGUUUAAUACAGCAUGUGTT 457 103493 GGCAUAUUCCACUGAUUACTT 458   1176 GGUCCACAAGGCAGUGCUGTT 459 111523 CGAAGUUAUCAGAGAUGCUTT 460  33700 GGAGAAAUGACCUCAUUUUTT 461   2167 GGAAUGAUCCAUACUGAAATT 462 105854 GACAUCUUAGCCAGGAAAUTT 463  46281 GCUGCCUGUGGUGGUAAAATT 464  44894 GAAGCUGGAUACAGCAUAUTT 465  38041 GGAAAGACAACAAAUACUATT 466  42278 GUUAGCUUCAUAAUCUGUUTT 467 112472 GCCUAUCAAGACUUCAUUATT

TABLE 4 Expr. in Expr. in Expr. in Target siRNA HepG2 cells Huh cells primary Hepatocytes No. ID AffyID AvgExp AffyID AvgExp AffyID AvgExp 1 113613 221215_s_at 331 221215_s_at 1314 221215_s_at 1453 1 105742 221215_s_at 331 221215_s_at 1314 221215_s_at 1453 1 105202 221215_s_at 331 221215_s_at 1314 221215_s_at 1453 2 117853 207833_s_at 111 209399_at 254 207833_s_at 246 2 117852 207833_s_at 111 209399_at 254 207833_s_at 246 2 117851 207833_s_at 111 209399_at 254 207833_s_at 246 3 117417 209146_at 16655 209146_at 20005 209146_at 17401 3 117416 209146_at 16655 209146_at 20005 209146_at 17401 3 117418 209146_at 16655 209146_at 20005 209146_at 17401 4 42711 209970_x_at 1411 211366_x_at 155 211366_x_at 1281 4 42626 209970_x_at 1411 211366_x_at 155 211366_x_at 1281 5 10418 208727_s_at 5287 208727_s_at 16227 208727_s_at 6132 5 10505 208727_s_at 5287 208727_s_at 16227 208727_s_at 6132 6 118135 206155_at 690 206155_at 655 206155_at 4275 6 116839 206155_at 690 206155_at 655 206155_at 4275 7 105039 205927_s_at 139 205927_s_at 815 205927_s_at 167 7 105041 205927_s_at 139 205927_s_at 815 205927_s_at 167 8 1147 207178_s_at 64 207178_s_at 209 207178_s_at 348 8 1243 207178_s_at 64 207178_s_at 209 207178_s_at 348 9 8225 203040_s_at 1156 203040_s_at 1002 203040_s_at 1214 9 117844 203040_s_at 1156 203040_s_at 1002 203040_s_at 1214 10 106087 201413_at 6700 201413_at 12772 201413_at 4948 10 106089 201413_at 6700 201413_at 12772 201413_at 4948 11 121011 212531_at 51 212531_at 33 212531_at 1215 11 121012 212531_at 51 212531_at 33 212531_at 1215 12 1766 206825_at 108 206825_at 168 206825_at 81 12 1947 206825_at 108 206825_at 168 206825_at 81 13 142836 204284_at 909 204284_at 1704 204284_at 6326 13 142834 204284_at 909 204284_at 1704 204284_at 6326 14 1547 203218_at 2388 203218_at 2503 203218_at 927 14 1452 203218_at 2388 203218_at 2503 203218_at 927 15 1699 211370_s_at 315 211370_s_at 439 204756_at 209 15 118252 211370_s_at 315 211370_s_at 439 204756_at 209 16 43916 16 43820 17 402 203856_at 1496 203856_at 2144 203856_at 511 17 401 203856_at 1496 203856_at 2144 203856_at 511 18 117695 230084_at 91 230084_at 36 230084_at 249 18 117693 230084_at 91 230084_at 36 230084_at 249 19 118261 209333_at 171 209333_at 242 209333_at 194 19 118260 209333_at 171 209333_at 242 209333_at 194 20 5146 221312_at 15 221312_at 17 221312_at 10 20 5237 221312_at 15 221312_at 17 221312_at 10 21 828 201939_at 168 201939_at 218 201939_at 8886 21 829 201939_at 168 201939_at 218 201939_at 8886 22 19104 202458_at 91 202458_at 538 202458_at 669 22 19196 202458_at 91 202458_at 538 202458_at 669 23 103354 216945_x_at 282 213534_s_at 185 216945_x_at 35 23 978 216945_x_at 282 213534_s_at 185 216945_x_at 35 24 2240 221329_at 31 221329_at 40 221329_at 85 24 2061 221329_at 31 221329_at 40 221329_at 85 25 20115 220334_at 52 220334_at 33 220334_at 43 25 20024 220334_at 52 220334_at 33 220334_at 43 26 118397 228098_s_at 1559 228098_s_at 505 228098_s_at 911 26 118398 228098_s_at 1559 228098_s_at 505 228098_s_at 911 27 104835 1559261_a_at 156 1559261_a_at 104 1559261_a_at 158 27 104830 1559261_a_at 156 1559261_a_at 104 1559261_a_at 158 28 119221 205750_at 260 205750_at 853 205750_at 413 29 105141 221654_s_at 5010 221654_s_at 3066 221654_s_at 3157 30 122236 225783_at 4314 225787_at 1528 225783_at 3676 31 43781 224049_at 126 224049_at 65 224049_at 177 32 103636 212533_at 2413 212533_at 3573 212533_at 6944 33 45922 236407_at 153 208514_at 45 236407_at 353 34 117371 207438_s_at 1946 207438_s_at 1674 207438_s_at 847 35 111157 200901_s_at 5755 200901_s_at 3087 200900_s_at 1971 36 38979 232647_at 94 232647_at 141 232647_at 118 37 121933 227614_at 139 227614_at 44 227614_at 660 38 119829 222839_s_at 631 222839_s_at 476 224427_s_at 559 39 19471 203105_s_at 1802 203105_s_at 980 203105_s_at 1867 40 120442 212296_at 8661 212296_at 14932 212296_at 9585 41 105154 222462_s_at 507 222462_s_at 726 222462_s_at 578 42 6196 224285_at 30 224285_at 25 224285_at 26 43 105753 219058_x_at 74 219058_x_at 156 219058_x_at 101 44 21895 206868_at 207 206868_at 108 206868_at 154 45 120445 214369_s_at 262 214369_s_at 120 214369_s_at 266 46 111807 205174_s_at 1889 205174_s_at 31 205174_s_at 135 47 1721 216220_s_at 127 216220_s_at 121 216220_s_at 170 48 1774 208048_at 60 208048_at 28 208048_at 50 49 117712 50 1795 212070_at 395 212070_at 69 212070_at 187 51 117084 203537_at 1771 203537_at 1683 203537_at 1339 52 119926 214951_at 19 214951_at 55 214951_at 26 53 9067 210505_at 52 210505_at 30 210505_at 53 54 121179 234436_x_at 30 234436_x_at 21 234841_x_at 24 55 38327 56 111813 207641_at 82 207641_at 122 207641_at 150 57 107569 210609_s_at 836 210609_s_at 993 210609_s_at 1914 58 10560 206651_s_at 3972 206651_s_at 2798 206651_s_at 23261 59 10235 204732_s_at 330 204732_s_at 400 210995_s_at 504 60 104127 221337_s_at 10 221337_s_at 35 221337_s_at 34 61 112077 225440_at 981 223184_s_at 1081 225440_at 1232 62 105010 202450_s_at 253 202450_s_at 251 202450_s_at 203 63 4154 229105_at 86 229105_at 559 229105_at 683 64 40980 213922_at 127 213922_at 120 1554293_at 130 65 120756 213036_x_at 220 207521_s_at 31 207521_s_at 66 66 1627 210105_s_at 1206 210105_s_at 472 210105_s_at 283 67 122128 68 2207 69 4633 211438_at 7 211438_at 11 211438_at 32 70 119952 225835_at 899 225835_at 2939 204404_at 447 71 105325 205624_at 36 205624_at 21 205624_at 16 72 112330 226314_at 444 226314_at 340 226314_at 93 73 121576 205320_at 150 205320_at 138 205320_at 205 74 117799 231424_at 23 231424_at 179 214389_at 29 75 104458 211662_s_at 14795 211662_s_at 10012 211662_s_at 25082 76 112453 209240_at 2917 209240_at 3035 209240_at 1612 77 121337 205046_at 489 205046_at 1193 205046_at 9 78 110844 202315_s_at 345 226602_s_at 477 202315_s_at 388 79 119422 1560445_x_at 212 1560445_x_at 177 1560445_x_at 171 80 119276 208649_s_at 3384 208649_s_at 6397 208649_s_at 4972 81 118817 218440_at 1546 218440_at 2214 218440_at 1212 82 118114 224002_s_at 509 224002_s_at 1031 224002_s_at 460 83 118462 202962_at 265 202962_at 724 202962_at 582 84 46510 1553222_at 153 1553222_at 145 1553222_at 68 85 119129 202517_at 100 202517_at 38 202517_at 66 86 119399 234513_at 24 234513_at 27 234513_at 27 87 122166 210027_s_at 6714 210027_s_at 5325 210027_s_at 7170 88 45063 211226_at 53 211226_at 83 211226_at 96 89 117601 220371_s_at 249 220371_s_at 238 220371_s_at 168 90 118446 209408_at 1715 209408_at 2483 209408_at 112 91 18240 224300_x_at 183 224300_x_at 416 223702_x_at 1248 92 104559 204811_s_at 169 204811_s_at 200 204811_s_at 303 93 1407 202530_at 2293 202530_at 2001 211561_x_at 1358 94 119077 201765_s_at 2783 201765_s_at 1993 201765_s_at 1371 95 1371 219257_s_at 1030 219257_s_at 394 219257_s_at 508 96 106537 202325_s_at 17972 202325_s_at 19536 202325_s_at 16304 97 120500 205811_at 605 205811_at 852 205811_at 839 98 111654 207085_x_at 147 211286_x_at 47 211287_x_at 131 99 118718 209723_at 596 209723_at 3656 209723_at 910 100 120608 220418_at 16 220418_at 22 220418_at 8 101 142253 213465_s_at 4176 213465_s_at 1986 213465_s_at 2635 102 111081 212293_at 2245 212293_at 2410 212293_at 1664 103 103786 200075_s_at 2999 200075_s_at 2534 200075_s_at 3897 104 121943 219248_at 819 219248_at 569 219248_at 654 105 121806 223597_at 103 223597_at 65 223597_at 70 106 15527 233547_x_at 38 233547_x_at 34 208396_s_at 37 107 143005 204612_at 26 204612_at 1000 204612_at 54 108 110607 205498_at 11 205498_at 217 205498_at 1373 109 107834 210852_s_at 121 214829_at 254 214829_at 131 110 121163 111 118522 204411_at 193 204411_at 92 204411_at 39 112 120179 211285_s_at 4332 211285_s_at 3412 211285_s_at 4322 113 34999 225411_at 5315 225411_at 1649 225411_at 583 114 6091 223767_at 797 223767_at 30 223767_at 10 115 103829 116 119396 202548_s_at 1872 202548_s_at 827 202548_s_at 1083 117 8816 209420_s_at 328 209420_s_at 296 209420_s_at 561 118 15339 207800_at 26 207800_at 18 207800_at 32 119 29459 218480_at 498 218480_at 368 231857_s_at 133 120 16059 214518_at 93 214518_at 126 214518_at 187 121 104173 209765_at 139 221128_at 69 209765_at 260 122 120611 218186_at 38 218186_at 13 218186_at 26 123 142929 201834_at 543 201834_at 744 201835_s_at 760 124 35220 208912_s_at 1547 208912_s_at 1273 208912_s_at 1142 125 119469 204867_at 1286 204867_at 1727 204867_at 733 126 121471 205263_at 2961 205263_at 3849 205263_at 2914 127 122003 229253_at 786 229253_at 954 229253_at 911 128 114058 200602_at 2782 214953_s_at 4350 200602_at 2082 129 117031 206662_at 9085 206662_at 2432 206662_at 11092 130 110906 203917_at 6573 203917_at 8611 203917_at 4681 131 119517 132 114048 133 809 206028_s_at 3023 206028_s_at 543 211913_s_at 326 134 137195 212625_at 1388 212625_at 1037 212625_at 554 135 118341 229106_at 223 229106_at 168 229106_at 451 136 46319 223284_at 281 223284_at 104 223284_at 56 137 7204 204401_at 2183 204401_at 16 204401_at 63 138 119081 209166_s_at 3051 209166_s_at 743 209166_s_at 257 139 745 40420_at 1233 40420_at 159 40420_at 522 140 119216 207618_s_at 689 207618_s_at 626 207618_s_at 1792 141 117277 207408_at 162 207408_at 165 207408_at 201 142 14775 202298_at 19882 202298_at 9707 202298_at 12823 143 119182 211733_x_at 9927 201339_s_at 15103 211733_x_at 9050 144 1286 218942_at 935 218942_at 1495 218942_at 952 145 1961 214605_x_at 66 214605_x_at 50 214605_x_at 43 146 119782 203865_s_at 751 203865_s_at 203 203865_s_at 148 147 135366 206092_x_at 179 206092_x_at 167 206092_x_at 111 148 42362 221327_s_at 34 221327_s_at 31 221327_s_at 84 149 12155 225418_at 1120 225418_at 1413 203149_at 1037 150 11 210838_s_at 57 210838_s_at 53 210838_s_at 31 151 7881 210944_s_at 250 210944_s_at 103 210944_s_at 273 152 10428 201097_s_at 12304 201097_s_at 11471 201097_s_at 19811 153 16123 201036_s_at 2233 201036_s_at 2352 201036_s_at 3584 154 1049 210346_s_at 1129 210346_s_at 506 210346_s_at 1149 155 919 214398_s_at 639 204549_at 163 214398_s_at 180 156 121066 56197_at 1567 56197_at 946 56197_at 1354 157 105169 203356_at 1488 203356_at 7040 203356_at 1403 158 36311 223809_at 222 223809_at 45 223809_at 57 159 5884 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TABLE 5 Target Target Transferrin Transferrin Transferrin Transferrin No Symbol Gene ID siRNA ID Run1 Mean % Run1 SD % Runs Mean % Run2 SD % 2 HLCS 3141 117851 146.8 47.4 2 HLCS 3141 117852 164.4 33.1 2 HLCS 3141 117853 113.3 6.5 3 SC4MOL 6307 117416 178.7 13.0 3 SC4MOL 6307 117417 184.0 17.9 3 SC4MOL 6307 117418 109.6 26.3 9 HMBS 3145 8225 260.9 18.6 9 HMBS 3145 117844 239.0 9.7 10 HSD17B4 3295 106087 451.0 83.7 10 HSD17B4 3295 106089 178.8 18.3 208.0 18.2 11 LCN2 3934 121011 43.9 7.0 11 LCN2 3934 121012 54.6 14.4 13 PPP1R3C 5507 142834 107.6 12.5 13 PPP1R3C 5507 142836 104.7 18.5 16 TPI1 7167 43820 108.4 10.7 16 TPI1 7167 43916 204.2 36.6 18 SLC30A2 7780 117693 172.2 25.4 18 SLC30A2 7780 117695 316.7 51.7 19 ULK1 8408 118260 126.3 27.9 19 ULK1 8408 118261 333.2 56.7 22 SPUVE 11098 19104 130.0 11.1 142.7 2.7 22 SPUVE 11098 19196 176.5 18.5 123.6 4.4 22 SPUVE 11098 212941 79.5 13.3 74.8 2.4 22 SPUVE 11098 212942 221.5 53.8 26 MYLIP 29116 118397 134.7 26.9 26 MYLIP 29116 118398 98.0 10.8 27 PKD1L2 114780 104830 159.8 27.5 168.3 17.1 27 PKD1L2 114780 104835 250.0 50.2 28 BPHL 670 119221 230.3 16.3 28 BPHL 670 214767 145.0 4.8 29 USP3 9960 105141 478.2 66.2 29 USP3 9960 214567 83.3 20.0 31 KCNK17 89822 43781 375.9 21.1 346.4 3.1 31 KCNK17 89822 212814 51.8 3.4 31 KCNK17 89822 212815 70.7 17.3 32 WEE1 7465 212739 199.1 56.6 295.1 20.4 34 RNUT1 10073 117371 328.2 25.7 34 RNUT1 10073 214780 72.8 6.7 35 M6PR 4074 111157 133.3 16.5 35 M6PR 4074 214744 85.5 7.0 36 MGC39650 147011 38979 320.9 46.8 36 MGC39650 147011 214871 76.8 15.5 37 FLJ22761 80201 121933 308.7 45.1 37 FLJ22761 80201 214839 183.5 26.0 38 PAPOLG 64895 119829 52.3 1.9 38 PAPOLG 64895 214280 272.9 26.9 190.1 3.7 39 DNM1L 10059 19471 151.2 27.2 39 DNM1L 10059 214799 104.7 12.7 43 LCN7 64129 105753 197.2 25.5 43 LCN7 64129 214577 52.2 10.8 45 RASGRP2 10235 120445 175.9 13.8 45 RASGRP2 10235 214874 73.7 8.9 51 PRPSAP2 5636 117084 54.0 6.8 51 PRPSAP2 5636 214750 117.4 9.9 52 SLC26A10 65012 119926 248.0 13.3 52 SLC26A10 65012 214589 181.1 12.6 56 TNFRSF13B 23495 111813 248.5 28.7 56 TNFRSF13B 23495 214802 105.0 21.4 62 CTSK 1513 105010 460.6 63.8 62 CTSK 1513 214550 108.4 6.9 72 D4ST-1 113189 112330 247.0 28.3 262.6 18.6 72 D4ST-1 113189 214285 137.6 12.9 233.0 21.2 73 APCL 10297 121576 194.5 25.8 73 APCL 10297 214783 172.5 12.8 79 ARHGEF1 9138 119422 217.2 35.9 79 ARHGEF1 9138 214561 162.0 29.3 81 MCCC1 56922 118817 48.0 2.0 81 MCCC1 56922 214276 57.6 16.2 81.5 10.0 88 GALR2 8811 212858 125.8 23.7 143.6 28.3 117 SMPD1 6609 8816 112.3 4.2 117 SMPD1 6609 212695 136.7 10.0 143 SCP2 6342 119182 191.9 30.7 143 SCP2 6342 214903 125.4 29.7 163 CCM1 889 15563 87.6 18.2 163 CCM1 889 214883 213.3 51.5 171 PAFAH2 5051 119066 70.8 8.2 171 PAFAH2 5051 214710 98.7 18.0 180 GAD2 2572 9108 165.2 19.8 180 GAD2 2572 214716 285.5 18.1 205 HTR2C 3358 144642 87.8 2.7 205 HTR2C 3358 212705 127.3 7.6 215 LOC345667 11174 212853 161.3 35.3 237 GPR3 2827 1785 70.9 19.6 56.7 10.5 237 GPR3 2827 212766 87.6 13.8 240 FLJ32389 126393 122036 194.9 22.0 240 FLJ32389 126393 214864 110.7 20.1 241 SERPINA7 6906 118553 182.3 10.3 241 SERPINA7 6906 214548 337.9 11.6 242 DCTD 1635 119612 440.5 32.2 242 DCTD 1635 214555 152.9 17.2 261 ACLY 47 116939 106.8 3.2 261 ACLY 47 214886 92.2 13.1 273 AGXT2L1 64850 112237 60.3 9.8 273 AGXT2L1 64850 214281 102.0 16.9 147.6 35.4 291 ARSE 415 119012 185.2 31.3 291 ARSE 415 214706 353.7 43.1 292 ITGB8 3696 11202 95.6 16.5 292 ITGB8 3696 214742 225.5 8.7 306 NR2F2 7026 5922 167.0 32.8 168.5 44.3 306 NR2F2 7026 212809 49.5 7.4 309 ADAM18 8749 212787 269.8 19.3 224.5 21.0 334 ARHGEF2 9181 119230 340.3 107.3 334 ARHGEF2 9181 214562 279.4 26.5 352 PRP2 134285 43202 186.8 28.5 352 LOC134285 134285 128215 98.5 24.2 352 LOC134285 134285 212841 43.0 1.5 363 PLA2R1 22925 108254 173.7 27.0 363 PLA2R1 22925 214723 215.6 31.0 390 CREB5 9586 116760 63.1 5.7 390 CREB5 9586 214882 197.1 14.8 413 FEN1 2237 121476 107.0 28.6 413 FEN1 2237 214763 116.1 13.0 435 PRSS15 9361 105664 141.2 5.6 128.9 5.1 435 PRSS15 9361 212757 93.3 13.2 435 PRSS15 9361 212758 88.9 10.6 441 SYNJ1 8867 104702 388.9 7.4 354.9 53.3 441 SYNJ1 8867 212746 10.7 1.1 441 SYNJ1 8867 212747 129.0 12.2 459 PCYT1B 9468 111523 146.8 16.0 459 PCYT1B 9468 214260 183.3 27.0 197.7 14.8 486 FLJ21736 79984 119838 275.3 13.8 486 FLJ21736 79984 235619 216.7 51.0 489 GPR10 2834 103837 141.9 10.0 489 GPR10 2834 235614 171.2 8.9 495 KIR2DS1 3806 212646 224.1 17.0 495 KIR2DS1 3806 235634 140.4 10.0 496 KIR2DS3 3808 213159 214.4 25.8 496 KIR2DS3 3808 235633 87.8 12.8 498 LOC135896 135896 213242 259.7 7.7 498 LOC135896 135896 235629 49.9 7.0 506 MOXD1 26002 111923 193.5 17.0 506 MOXD1 26002 235615 178.9 27.0 507 MPN2 339501 113991 45.7 5.8 507 MPN2 339501 235626 302.7 27.3 514 PEPD 5184 105302 313.2 67.0 353.2 64.4 514 PEPD 5184 212688 213.9 14.9

TABLE 6 Target Target Gene siRNA siRNA LDL-Dil run1 LDL-Dil LDL-Dil run2 LDL-Dil run2 LDL-Dil run3 LDL-Dil run3 No Symbol Id ID conc. Mean % run1 SD % Mean % SD % Mean % SD % 2 HLCS 3141 117852 10 414.5 93.1 451 99.6 126.3 22.6 2 HLCS 3141 117852 30 591.2 39.7 631.6 62.1 233 47.9 2 HLCS 3141 117852 100 502.9 112.1 720.9 143 266.9 17.7 2 HLCS 3141 117853 10 379.4 81.1 421.3 106.9 363.3 37 2 HLCS 3141 117853 30 590.7 78 572.4 60.8 418.6 42.8 2 HLCS 3141 117853 100 737.3 36.3 930.2 178.1 787.2 64.5 3 SC4MOL 6307 117417 10 658.1 147.8 612.5 115.7 421.4 17.9 3 SC4MOL 6307 117417 30 918.8 50.2 509.2 148.3 179.9 9 3 SC4MOL 6307 117417 100 1341.9 148.3 857.9 190.6 436.9 155.6 3 SC4MOL 6307 117418 10 420.1 66.8 596.2 63.5 258.1 55.6 3 SC4MOL 6307 117418 30 703.9 6.8 670.7 26.5 164.6 3.6 3 SC4MOL 6307 117418 100 912.2 96.2 786 22.6 351.9 38.9 4 CASP1 834 42626 10 300.7 27 210.1 64.5 242.6 74.3 4 CASP1 834 42626 30 275.3 70.1 234.8 13.6 274.5 30.8 4 CASP1 834 42626 100 343.6 87 388.3 39 452.7 128 4 CASP1 834 42711 10 336.7 70.2 351.8 54.1 360.3 127.5 4 CASP1 834 42711 30 642.9 45.3 377.6 51.6 469.1 74.9 4 CASP1 834 42711 100 860.1 70.8 623.9 70.3 469.7 118.1 7 CTSE 1510 105039 10 521.4 15.8 318.4 63.9 500.9 99.9 7 CTSE 1510 105039 30 647 131.3 674.6 106.7 631.5 36.3 7 CTSE 1510 105039 100 695.2 29.7 1494.5 191.2 832.3 122.9 7 CTSE 1510 105041 10 148.4 8 164.1 27.1 184.4 61.9 7 CTSE 1510 105041 30 198.1 9.5 208.5 37.5 179.9 41.2 7 CTSE 1510 105041 100 229.2 67 354.7 68.4 231.7 13.2 8 FRK 2444 1147 10 282.1 87.5 255.4 78.7 221 26.4 8 FRK 2444 1147 30 321.9 37.3 350.1 12.7 256 25.5 8 FRK 2444 1147 100 508.8 22.1 431.5 33.7 270.3 52.8 8 FRK 2444 1243 10 268.4 90.6 275.7 75.3 241.2 21.5 8 FRK 2444 1243 30 267.4 7.4 268.5 12.6 279.1 24.8 8 FRK 2444 1243 100 310.3 17.7 497.1 60.1 485.5 130.5 9 HMBS 3145 8225 10 304.7 63.7 291.6 64.1 287.2 24.9 9 HMBS 3145 8225 30 448.8 7.8 368.2 78.1 287.4 39.1 9 HMBS 3145 8225 100 562.9 122.7 530.8 93.9 413.3 32.8 9 HMBS 3145 117844 10 194 27.8 199.3 26.1 166.2 21 9 HMBS 3145 117844 30 204.8 7.6 187.5 30.6 171.1 16.9 9 HMBS 3145 117844 100 152.4 21 253.1 37.2 185.9 52.3 10 HSD17B4 3295 106087 10 397 56.5 390.6 127.4 261.1 38.3 10 HSD17B4 3295 106087 30 479.9 47.8 502.6 98.4 320.6 23.9 10 HSD17B4 3295 106087 100 552.6 33.8 682.4 115.5 403.2 50 10 HSD17B4 3295 106089 10 239.4 53 171.9 47.3 127.2 23.8 10 HSD17B4 3295 106089 30 380.8 18.4 243.2 29.9 168 33.2 10 HSD17B4 3295 106089 100 288 35.5 272.1 11.8 176.4 22.6 12 OXTR 5021 1766 10 605.7 38.7 316.3 40.2 233.3 41.1 12 OXTR 5021 1766 30 703 42.5 389.3 61.8 238.6 16.5 12 OXTR 5021 1766 100 720.8 80.2 596.9 114.3 253.2 42.9 12 OXTR 5021 1947 10 432.6 55.5 176.9 51.4 241.6 65.8 12 OXTR 5021 1947 30 271.8 6.5 208.7 16 260.3 51.7 12 OXTR 5021 1947 100 354.6 96.8 409.4 60.1 373.2 89 16 TPI1 7167 43820 10 230.6 100.9 243 11.4 173.2 13.7 16 TPI1 7167 43820 30 326.7 39.3 336.8 56.6 240.9 20.8 16 TPI1 7167 43820 100 276.9 51.3 569.4 95.5 255 79.5 16 TPI1 7167 43916 10 590.4 629.2 381.4 37.9 273 12 16 TPI1 7167 43916 30 700.7 40.5 546 123.3 354.1 37.7 16 TPI1 7167 43916 100 754.8 79.3 969.1 187.7 398.4 48.5 18 SLC30A2 7780 117693 10 261.6 40.1 218.4 29.1 145.4 30.8 18 SLC30A2 7780 117693 30 362.7 12.5 309 59.2 185.2 25.2 18 SLC30A2 7780 117693 100 420.8 37.8 562.7 62.5 312.5 67.9 18 SLC30A2 7780 117695 10 581.1 50.6 305.6 36.4 311 19.8 18 SLC30A2 7780 117695 30 622 92.2 399.7 46.6 365.5 23.4 18 SLC30A2 7780 117695 100 665.6 39 680.6 136.2 553.5 28.2 19 ULK1 8408 118260 10 283.6 98.5 251.3 28.1 219.3 5.6 19 ULK1 8408 118260 30 356.4 39.6 346.2 71.5 269.1 32.8 19 ULK1 8408 118260 100 428.9 44.8 471.6 54.1 319.7 29.1 19 ULK1 8408 118261 10 336.4 110.4 475.9 48.1 134.5 6.2 19 ULK1 8408 118261 30 750 96 715.4 172 444.1 95 19 ULK1 8408 118261 100 1009.5 162.2 1610.5 116 1007.2 271 22 SPUVE 11098 19104 10 357.4 47.1 323.6 82.7 314.4 46.3 22 SPUVE 11098 19104 30 757.4 42.5 598.2 91.7 412.9 53.1 22 SPUVE 11098 19104 100 713 51 1405 174.5 495.9 51.7 22 SPUVE 11098 19196 10 209.1 72.2 201.2 57.3 255.7 17 22 SPUVE 11098 19196 30 351.9 32.4 242.2 49.3 147.2 20.5 22 SPUVE 11098 19196 100 350.6 35.1 430.5 48.4 451.8 18.7 27 PKD1L2 114780 104830 10 203.9 24.1 192.5 35.9 126.6 18.3 27 PKD1L2 114780 104830 30 274 51.9 199.8 31.6 179.7 21.6 27 PKD1L2 114780 104830 100 249.7 24.6 305.4 19.6 255.4 31.3 27 PKD1L2 114780 104835 10 383.9 45.3 526.7 46.2 538.4 68 27 PKD1L2 114780 104835 30 517.1 35.4 660.5 114.7 489.6 28.8 27 PKD1L2 114780 104835 100 716.7 115.9 964.3 127.2 1060.5 161.7 39 DNM1L 10059 19471 10 280.6 61.3 424 18.7 359 48 39 DNM1L 10059 19471 30 484.8 63 541.7 78.7 403.4 66.5 39 DNM1L 10059 19471 100 725.2 41.8 802.2 68.3 539.9 40.2 39 DNM1L 10059 214799 10 378.6 39.7 460.4 86.7 291.9 31.1 39 DNM1L 10059 214799 30 428.8 57 515.3 25.3 332.7 17 39 DNM1L 10059 214799 100 454.6 57.4 615.1 245.1 385.2 45.7 88 GALR2 8811 44971 10 996.6 184.4 520.3 73.8 466.7 101 88 GALR2 8811 44971 30 891.6 91.1 606.4 126.9 439.5 43.2 88 GALR2 8811 44971 100 1077.3 28.1 1020 150.9 723.4 98.9 88 GALR2 8811 45063 10 67.2 16.1 103.6 2.7 98.6 57.3 88 GALR2 8811 45063 30 77.8 17.1 110.3 33.3 91 12.1 88 GALR2 8811 45063 100 63.4 9.9 122.8 28.6 113.4 7.6 143 SCP2 6342 117110 10 398 81.2 143 SCP2 6342 117110 30 169.3 21.6 143 SCP2 6342 117110 100 152.6 40.4 143 SCP2 6342 119182 10 689.2 495.8 432.8 50.8 294.2 74.8 143 SCP2 6342 119182 30 1117.7 310.7 648.3 78.3 399.5 67.5 143 SCP2 6342 119182 100 958 112.2 1365.2 233.3 521.1 101.1 171 PAFAH2 5051 119066 10 277.3 83.4 315.2 48.9 270.7 33.2 171 PAFAH2 5051 119066 30 464 26.4 368.9 33.5 309.9 16.9 171 PAFAH2 5051 119066 100 612.7 11.6 559.8 132 382.7 103.9 171 PAFAH2 5051 214710 10 284.8 65.8 336.5 70.8 235 27.4 171 PAFAH2 5051 214710 30 415.4 45.3 398.6 75.8 230.2 36 171 PAFAH2 5051 214710 100 322.9 27.6 541.8 36 332 24.5 180 GAD2 2572 9108 10 302.3 49.7 266.4 65.3 282.5 35.8 180 GAD2 2572 9108 30 490.1 51.1 356 54.7 380.3 60.6 180 GAD2 2572 9108 100 527.8 29.3 212.2 40 521.8 67.1 180 GAD2 2572 214716 10 309.9 104.4 294.8 45.6 129 15.1 180 GAD2 2572 214716 30 415.6 87.9 273.3 16 275.8 43.4 180 GAD2 2572 214716 100 434.7 17.8 386.5 108.7 278.6 91.8 205 HTR2C 3358 1852 10 454.3 107.4 447.3 10.3 429.1 74.9 205 HTR2C 3358 1852 30 565.3 137.7 596.6 92.7 568 44.1 205 HTR2C 3358 1852 100 437.6 75.9 1158.7 227.7 774.3 237.8 205 HTR2C 3358 1940 10 86.8 22.7 136.7 11.5 124.1 38.9 205 HTR2C 3358 1940 30 105.4 17.1 112.6 12.9 155.5 21.6 205 HTR2C 3358 1940 100 83.9 15.1 156.3 21.1 199.1 60.9 215 LOC345667 345667 104231 10 301.2 53.3 317.5 38.1 302.1 93.8 215 LOC345667 345667 104231 30 353.7 24 377.5 36.2 309 49.5 215 LOC345667 345667 104231 100 490.6 33.8 635.2 35.6 461.4 36 215 LOC345667 345667 212853 10 436.6 140.7 489.6 74.1 371.3 4.2 215 LOC345667 345667 212853 30 649.3 82.1 580.8 82.2 523.5 97.5 215 LOC345667 345667 212853 100 952.9 107.5 873.4 112.1 932.2 144.8 237 GPR3 2827 1785 10 803.5 125.7 389.1 66.8 329 76.1 237 GPR3 2827 1785 30 1236.3 235.5 577.6 78.8 346.8 26.3 237 GPR3 2827 1785 100 1205.3 182 1253.8 182.6 490.4 32.5 237 GPR3 2827 212766 10 151.3 38.7 154.2 26.8 123.1 4.5 237 GPR3 2827 212766 30 185.3 57.4 171.4 18.5 180.3 4.5 237 GPR3 2827 212766 100 137.5 40.8 152.3 53.3 191.1 39.3 242 DCTD 1635 119612 10 420.5 55 469.3 154.6 125.7 11.9 242 DCTD 1635 119512 30 779.7 68 568.5 84.9 428.5 107 242 DCTD 1635 119612 100 846.4 93.1 1253.4 63.9 593.4 84.1 242 DCTD 1635 214555 10 243.8 68.8 222.4 36.5 189.4 37.2 242 DCTD 1635 214555 30 281.3 38.2 242.3 20.6 240.6 30.8 242 DCTD 1635 214555 100 321.5 71.7 406 79.3 353 7.5 261 ACLY 47 116939 10 455.5 44.1 675.6 114 366.8 82.7 261 ACLY 47 116939 30 552.2 212.1 763.5 18.7 474.8 48.6 261 ACLY 47 116939 100 845.5 113.3 1174.6 41 957.5 179 261 ACLY 47 116940 10 291.9 16.8 261 ACLY 47 116940 30 351.9 4.6 261 ACLY 47 116940 100 448.9 62.3 273 AGXT2L1 64850 112236 10 232.7 60.7 273 AGXT2L1 64850 112236 30 249.9 26.5 273 AGXT2L1 64850 112236 100 283.1 52.9 273 AGXT2L1 64850 112237 10 347.6 251.7 352.3 29.2 327.5 45.7 273 AGXT2L1 64850 112237 30 505.2 87.6 415.2 51.4 326.4 29 273 AGXT2L1 64850 112237 100 513.9 67.3 524.4 90.5 448.5 60.9 291 ARSE 415 119012 10 226.3 41.4 241.9 35.3 243 24.8 291 ARSE 415 119012 30 497.1 20.2 355.5 43.9 175.4 12.2 291 ARSE 415 119012 100 501.9 23.4 468.1 52.1 364 107.9 291 ARSE 415 214706 10 252.7 63.8 330.9 48 327.3 43.2 291 ARSE 415 214706 30 458.6 92.1 297.7 36.4 370.2 59.7 291 ARSE 415 214706 100 439 55.5 583.1 37.9 539.5 173.4 306 NR2F2 7026 5922 10 286.8 46 251.8 35.5 262.3 23.5 306 NR2F2 7026 5922 30 452.2 40.5 402.6 34.1 299.8 47.5 306 NR2F2 7026 5922 100 557.1 54.2 753.1 132.2 415.2 55.7 306 NR2F2 7026 45374 10 298.6 69.2 339.9 73.2 356.6 87.2 306 NR2F2 7026 45374 30 485.8 28.6 481.3 32.3 413.6 36.8 306 NR2F2 7026 45374 100 640.1 69.3 672.3 97.4 655.9 208 309 ADAM18 8749 104120 10 205 37.9 197.6 29.9 262 8.6 309 ADAM18 8749 104120 30 257.9 63.4 333.5 38.5 331.6 71.6 309 ADAM18 8749 104120 100 281.2 56.9 626.9 119.8 537.8 63.6 309 ADAM18 8749 212787 10 203 21.7 239 20.1 224.3 29.3 309 ADAM18 8749 212787 30 306.9 32 320.7 16.3 265.8 39.3 309 ADAM18 8749 212787 100 302.7 11.5 618.5 94.2 339 21.1 334 ARHGEF2 9181 119230 10 548.2 9.1 284.9 16.5 216.2 21.9 334 ARHGEF2 9181 119230 30 660.5 171.5 382 77.7 167.7 21.6 334 ARHGEF2 9181 119230 100 702.6 97.1 551.9 145.2 195.4 38.2 334 ARHGEF2 9181 214562 10 408.2 81 271.4 29.7 185 40 334 ARHGEF2 9181 214562 30 470.5 63.7 325.5 57 230.2 41.4 334 ARHGEF2 9181 214562 100 507.9 109.7 592 67.3 263.6 48.5 435 PRSS15 9361 105664 10 274.8 92.1 266.8 53.4 284.1 11.1 435 PRSS15 9361 105664 30 438.6 6.5 326.8 12.5 279.5 23.6 435 PRSS15 9361 105664 100 435.9 84.6 480 75 367.1 120.5 435 PRSS15 9361 212758 10 148.4 12.3 195.8 50.6 184.8 19 435 PRSS15 9361 212758 30 241.1 44.1 226 46.9 263.2 21.9 435 PRSS15 9361 212758 100 236.4 30.4 344.9 52.1 285.8 41.9 459 PCYT1B 9468 111523 10 293.2 57 238.5 49.4 429.8 56.8 459 PCYT1B 9468 111523 30 478.6 30 284.3 28.5 295.3 32.5 459 PCYT1B 9468 111523 100 439.9 24.8 529.4 101.8 555.2 147.4 459 PCYT1B 9468 214260 10 282.2 21.6 334.1 75.7 325.7 18.2 459 PCYT1B 9468 214260 30 429 35.2 397.2 24.2 299.9 39.5 459 PCYT1B 9468 214260 100 542.7 8.9 584.9 60 495.8 117.1 486 FLJ21736 79984 119838 10 233 32.4 486 FLJ21736 79984 119838 30 393.4 72.6 486 FLJ21736 79984 119838 100 525.6 153 486 FLJ21736 79984 235619 10 247.9 6.5 486 FLJ21736 79984 235619 30 354.5 137 486 FLJ21736 79984 235619 100 358.7 38.5 495 KIR2DS1 3806 212646 10 602 48.9 495 KIR2DS1 3806 212646 30 878.6 201.5 495 KIR2DS1 3806 212646 100 974.8 205.1 495 KIR2DS1 3806 235634 10 223.8 25.5 495 KIR2DS1 3806 235634 30 303.2 46.3 495 KIR2DS1 3806 235634 100 259.7 17.5 496 KIR2DS3 3808 213159 10 760.9 110.6 496 KIR2DS3 3808 213159 30 1006.6 156.5 496 KIR2DS3 3808 213159 100 909.4 190.6 496 KIR2DS3 3808 235633 10 177 42.2 496 KIR2DS3 3808 235633 30 191.7 64.8 496 KIR2DS3 3808 235633 100 178.8 35.4 506 MOXD1 26002 111923 10 383.4 57.9 506 MOXD1 26002 111923 30 486.8 106.6 506 MOXD1 26002 111923 100 749.4 363.5 506 MOXD1 26002 235615 10 191.5 36.4 506 MOXD1 26002 235615 30 237.6 108 506 MOXD1 26002 235615 100 303.6 22.6 514 PEPD 5184 105302 10 388 31.1 263.6 10.2 178.4 39.1 514 PEPD 5184 105302 30 441.3 124.9 293.3 67.3 220.3 70.9 514 PEPD 5184 105302 100 466.7 10.5 327.4 70.3 326.2 33.3 514 PEPD 5184 212688 10 234.7 113.3 239.4 42.8 172 9.9 514 PEPD 5184 212688 30 320.8 70.2 381.4 49.1 264.6 14.5 514 PEPD 5184 212688 100 281.9 30.1 664.8 157.3 316.6 41.4

TABLE 7 Target Target Gene siRNA Proliferation Proliferation Proliferation Proliferation Proliferation Proliferation No Symbol Id ID siRNA conc. run1 Mean % run1 SD % run2 Mean % run2 SD % run3 Mean % run3 SD % 2 HLCS 3141 117852 10 89.1 10.6 86.4 3.3 105.1 2.5 2 HLCS 3141 117852 30 73.5 1 88.3 3.1 106.3 2.6 2 HLCS 3141 117852 100 84.9 9.8 74.8 6.5 105.9 2.2 2 HLCS 3141 117853 10 136.3 22.1 108.8 2.7 102.2 0.7 2 HLCS 3141 117853 30 112.2 5.8 114.5 1.6 105.4 1 2 HLCS 3141 117853 100 116.1 14.2 119.3 2.4 103.1 0.6 3 SC4MOL 6307 117417 10 97 29.7 107.2 2.6 99.5 3.6 3 SC4MOL 6307 117417 30 98.8 1.2 103.7 5.5 101.5 2.7 3 SC4MOL 6307 117417 100 114.8 7.1 110.1 1.5 99.6 0.7 3 SC4MOL 6307 117418 10 85.8 14.3 103.1 6.7 96.7 2.4 3 SC4MOL 6307 117418 30 98.6 1 104.5 2 101.7 1.2 3 SC4MOL 6307 117418 100 110.7 11 106.6 3.2 96.1 1.8 4 CASP1 834 42626 10 101.2 49.9 110.6 5.1 97 9.7 4 CASP1 834 42626 30 98.8 5.3 108.2 3.8 99.6 4.3 4 CASP1 834 42626 100 120.7 3.3 109.2 3.8 100 2.3 4 CASP1 834 42711 10 73.9 31.3 102.5 6.4 105 7.4 4 CASP1 834 42711 30 83 2.4 105 5 97 2.7 4 CASP1 834 42711 100 107 5.6 99.9 5.9 102.1 4.7 7 CTSE 1510 105039 10 88.4 50.9 105.4 0.5 104 4.8 7 CTSE 1510 105039 30 103.4 4.1 97 2.8 102.3 7.4 7 CTSE 1510 105039 100 86.5 5 97.3 1.7 103.5 3.3 7 CTSE 1510 105041 10 117.5 21 104.8 2.7 100 4.1 7 CTSE 1510 105041 30 105.3 4.3 106 5.4 106.1 5 7 CTSE 1510 105041 100 118.2 12.3 106.5 1.8 99.9 4.6 8 FRK 2444 1147 10 91 32.6 101.1 4.7 99.9 2 8 FRK 2444 1147 30 89.5 1.5 102.9 5.9 96.2 2.2 8 ERK 2444 1147 100 110.7 2.9 100.1 1.9 98 1 8 FRK 2444 1243 10 134.5 25 111.7 7.1 109 2.2 8 FRK 2444 1243 30 106.5 8.3 115 5 105.8 1.3 8 FRK 2444 1243 100 122.8 10.8 119.6 7.4 105.6 1.4 9 HMBS 3145 8225 10 97.8 23.9 103.8 1.7 95.3 1.6 9 HMBS 3145 8225 30 84.7 8 103.3 1.8 95.4 0.4 9 HMBS 3145 8225 100 101.9 7.1 105.4 5.5 94.5 1.5 9 HMBS 3145 117844 10 99 26.1 101.7 1.6 100.5 2 9 HMBS 3145 117844 30 95.1 0.9 100.6 1.4 101.6 2.8 9 HMBS 3145 117844 100 107.2 5.7 105.8 4.3 98.6 1.4 10 HSD17B4 3295 106087 10 73 11.1 104.7 2.9 99.1 3 10 HSD17B4 3295 106087 30 93.7 1.8 105.7 3.2 95.9 0.4 10 HSD17B4 3295 106087 100 97.2 13.9 103.7 2.6 96.8 2.9 10 HSD17B4 3295 106089 10 83.5 22.4 100 1.8 114.3 1.6 10 HSD17B4 3295 106089 30 91.8 4.3 102.8 4.3 101.3 0.9 10 HSD17B4 3295 106089 100 108.2 13.2 104.9 4.7 106.8 2.2 12 OXTR 5021 1766 10 133.6 20.8 114.8 7.1 110.7 8.6 12 OXTR 5021 1766 30 102.8 1.9 108.1 5.1 106.1 6.8 12 OXTR 5021 1766 100 101 16.9 96.9 9.4 108.3 6 12 OXTR 5021 1947 10 87.2 35.8 104.4 4.1 114.8 6.6 12 OXTR 5021 1947 30 99.5 10.1 107.5 6.1 106.8 4.4 12 OXTR 5021 1947 100 113.5 14.2 111.3 1.8 110.1 4.4 16 TPI1 7167 43820 10 100.2 27.7 109.9 2.7 98.9 0.5 16 TPI1 7167 43820 30 102.2 3.7 105.6 3.8 97.6 1.8 16 TPI1 7167 43820 100 124.7 5.5 102 1.8 97.1 2.9 16 TPI1 7167 43916 10 108.9 25.7 112.1 4.1 97.2 1.7 16 TPI1 7167 43916 30 105.3 2.2 106.4 4.1 96.1 3.7 16 TPI1 7167 43916 100 124.7 4.9 101.8 3.4 96.5 2.1 18 SLC30A2 7780 117693 10 115.3 21.7 107.7 3.7 103.6 2.4 18 SLC30A2 7780 117693 30 88.2 10.2 112.2 1.4 103.8 0.5 18 SLC30A2 7780 117693 100 113.4 11.2 111.8 1.9 101.2 1.9 18 SLC30A2 7780 117695 10 115.3 21.7 108.5 6.1 94.9 1.5 18 SLC30A2 7780 117695 30 103.2 3.6 104.8 3.2 91.3 1.9 18 SLC30A2 7780 117695 100 113.4 11.2 100.7 2.8 87.3 2.5 19 ULK1 8408 118260 10 76.1 41.8 115 4.8 108.6 1.3 19 ULK1 8408 118260 30 108.9 7 117.3 3.1 105.2 0.7 19 ULK1 8408 118260 100 114.2 0.9 119.6 7.3 105.9 1.3 19 ULK1 8408 118261 10 86.2 39.5 110 5.3 103.6 2.5 19 ULK1 8408 118261 30 79.3 29.9 111 3.2 103.1 1.1 19 ULK1 8408 118261 100 90.9 11.1 107.2 2.5 102.8 1.5 22 SPUVE 11098 19104 10 104.9 26.2 112.5 2.3 100.6 1.3 22 SPUVE 11098 19104 30 104.3 3.8 114.7 0.9 99.6 3.5 22 SPUVE 11098 19104 100 115.4 10.3 115.3 2.1 101.1 2.1 22 SPUVE 11098 19196 10 119 11.3 114.3 4.9 105.8 2.6 22 SPUVE 11098 19196 30 103.9 13.7 117.7 2 100.9 1.9 22 SPUVE 11098 19196 100 110.3 17.8 121.9 4.9 102.6 3.2 27 PKD1L2 114780 104830 10 100.9 45.8 108.8 5.5 102.6 1 27 PKD1L2 114780 104830 30 102.4 1.9 113.9 3.2 99.3 0.8 27 PKD1L2 114780 104830 100 108.9 8.1 116.6 4.7 99.4 0.3 27 PKD1L2 114780 104835 10 88.4 50.9 106.7 2.2 100.4 2 27 PKD1L2 114780 104835 30 91.3 9.7 103.4 3 99.5 1.6 27 PKD1L2 114780 104835 100 86.5 5 105.2 1 98.7 1.3 39 DNM1L 10059 19471 10 100.2 27.7 107.4 5.4 113.1 2.6 39 DNM1L 10059 19471 30 107.7 1.5 111 7.3 108.6 1.3 39 DNM1L 10059 19471 100 124.7 5.5 113.2 4.2 111.6 2.7 39 DNM1L 10059 214799 10 94.6 20.6 99.4 6.5 97 1.1 39 DNM1L 10059 214799 30 95.8 5.6 103.3 1.4 93.9 2.1 39 DNM1L 10059 214799 100 105.5 12.2 100.2 6.8 94.5 1.5 88 GALR2 8811 44971 10 117.1 23.6 98 2.2 89 6.7 88 GALR2 8811 44971 30 99.5 2.6 96.5 1.6 90 3.4 88 GALR2 8811 44971 100 98.8 19.5 88.3 7.2 91.2 3.1 88 GALR2 8811 45063 10 76.1 41.8 111.4 3.3 105.8 10.6 88 GALR2 8811 45063 30 99.2 1.2 109.5 3.8 95 3.9 88 GALR2 8811 45063 100 114.2 0.9 106.1 2.9 98.3 7.9 143 SCP2 6342 117110 10 106.2 1.2 143 SCP2 6342 117110 30 105.3 1.6 143 SCP2 6342 117110 100 109 1.8 143 SCP2 6342 119182 10 101.2 49.9 112 3.9 98.4 1.1 143 SCP2 6342 119182 30 99.5 1.8 107 5.7 99.3 3.1 143 SCP2 6342 119182 100 120.7 3.3 105.6 2.2 96.5 1.8 171 PAFAH2 5051 119066 10 131.7 27.8 103.7 5.1 102.6 1.8 171 PAFAH2 5051 119066 30 100.1 8.9 101.5 6.5 99.9 0.8 171 PAFAH2 5051 119066 100 121.2 8.7 113.5 4.6 102.7 2.8 171 PAFAH2 5051 214710 10 110.2 34.7 105.6 2.9 104.2 1.9 171 PAFAH2 5051 214710 30 97.3 2.4 108.7 3.9 102.1 0.7 171 PAFAH2 5051 214710 100 116.8 5.8 108 3.3 100.5 0.9 180 GAD2 2572 9108 10 114.9 23.7 103.1 0.3 104.6 0.6 180 GAD2 2572 9108 30 82 11.4 102.2 5.3 101.7 2.2 180 GAD2 2572 9108 100 98 13 117.5 5.5 102 0.5 180 GAD2 2572 214716 10 84.1 47.7 99.5 6 105.4 2.1 180 GAD2 2572 214716 30 84.4 5.3 95.1 2.4 101.4 1.3 180 GAD2 2572 214716 100 109 4.3 97.2 5.6 99.7 2.2 205 HTR2C 3358 1852 10 73.6 33.8 102.5 2.1 106.5 5.2 205 HTR2C 3358 1852 30 104.3 1.8 100.4 7 97 6.9 205 HTR2C 3358 1852 100 108.4 5.1 99.3 1.4 99.5 2 205 HTR2C 3358 1940 10 109.4 39.8 100.6 5.2 97.7 7.4 205 HTR2C 3358 1940 30 99.2 3.1 93.4 4.8 96.4 6.2 205 HTR2C 3358 1940 100 123.1 7.6 92 3 100.7 2.8 215 LOC345667 345667 104231 10 94.5 35.5 103.8 1.5 100.5 7.2 215 LOC345667 345667 104231 30 98.6 2.2 104.9 4.5 94.2 5.2 215 LOC345667 345667 104231 100 119.8 5.9 106.8 4.6 99.2 3.5 215 LOC345667 345667 212853 10 73.6 33.8 107 5 107.7 1.7 215 LOC345667 345667 212853 30 100.1 6.7 111 1.4 104.9 1.9 215 LOC345667 345667 212853 100 108.4 5.1 112.3 4.7 107 1.8 237 GPR3 2827 1785 10 96.6 25.4 102.9 4.4 103.5 0.6 237 GPR3 2827 1785 30 101.2 0.3 97.8 4 100.4 2.6 237 GPR3 2627 1785 100 106.2 6.8 95.3 5 98.8 1.8 237 GPR3 2827 212766 10 87 8.2 100.4 3.9 107.1 2 237 GPR3 2827 212766 30 99.3 2.4 104.3 2.2 103.3 2 237 GPR3 2827 212766 100 112.2 5.5 102.3 2 103.1 2.3 242 DCTD 1635 119612 10 96.6 25.4 99.6 7.7 103.4 0.9 242 DCTD 1635 119612 30 99.9 3.2 102.5 7.8 96.1 1.4 242 DCTD 1635 119612 100 106.2 6.8 108.7 8.2 94.7 1.4 242 DCTD 1635 214555 10 109.4 39.8 111.4 4.3 104.5 1.8 242 DCTD 1635 214555 30 113.9 3.3 115.3 3.2 100.5 1.9 242 DCTD 1635 214555 100 123.1 7.6 117.6 4.3 98.6 2.2 261 ACLY 47 116939 10 111.7 21 107.4 2.8 101.9 0.8 261 ACLY 47 116939 30 102 8.1 109.6 2.4 100.8 1.7 261 ACLY 47 116939 100 107.1 17 111.7 3.3 98.4 1 261 ACLY 47 116940 10 99.8 1.2 261 ACLY 47 116940 30 97.3 2.2 261 ACLY 47 116940 100 98.4 2.3 273 AGXT2L1 64850 112236 10 106.7 1.2 273 AGXT2L1 64850 112236 30 102.2 0.2 273 AGXT2L1 64850 112236 100 104.3 2.2 273 AGXT2L1 64850 112237 10 73 11.1 103.7 6.5 99.9 2.8 273 AGXT2L1 64850 112237 30 104.9 1.9 110.3 3.2 98.2 1.3 273 AGXT2L1 64850 112237 100 97.2 13.9 105.6 1.4 99.1 0.2 291 ARSE 415 119012 10 141 29.1 106.2 2.5 104.3 1.7 291 ARSE 415 119012 30 94.2 4.2 109.6 2.4 99.8 1.1 291 ARSE 415 119012 100 115.2 15.1 116.1 3.3 100.7 1.2 291 ARSE 415 214706 10 117.3 24.2 96 4.8 104.8 1.5 291 ARSE 415 214706 30 73.6 8 95.6 4.7 96.6 0.7 291 ARSE 415 214706 100 72.1 8.8 86.4 4.5 95.7 0.8 306 NR2F2 7026 5922 10 120.8 24.1 109.2 0.8 108.3 0.4 306 NR2F2 7026 5922 30 99.1 6.6 110 1.8 102.1 1 306 NR2F2 7026 5922 100 107.1 12.2 113.4 7.9 104.5 0.9 306 NR2F2 7026 45374 10 86 18.2 112.1 4 109.8 6.4 306 NR2F2 7026 45374 30 112.1 6 114.1 2.2 105.9 7.2 306 NR2F2 7026 45374 100 129.2 9.4 116 2.1 104.4 8.1 309 ADAM18 8749 104120 10 111.7 21 114.8 9.2 102.8 9.8 309 ADAM18 8749 104120 30 102.1 1.8 106.2 3.3 97.3 9.7 309 ADAM18 8749 104120 100 107.1 17 97.3 5.6 98.6 2.1 309 ADAM18 8749 212787 10 90.2 28.8 90.9 1.9 102.3 0.7 309 ADAM18 8749 212787 30 98.5 1.2 99.4 2.1 101.7 1.6 309 ADAM18 8749 212787 100 98.4 8.8 99.5 4.6 100.6 1.4 334 ARHGEF2 9181 119230 10 104.9 26.2 97.2 7.9 108 2.7 334 ARHGEF2 9181 119230 30 99.1 3.4 93.1 7.7 100.3 0.2 334 ARHGEF2 9181 119230 100 115.4 10.3 92 1.8 106 1.6 334 ARHGEF2 9181 214562 10 74.4 39.6 105.8 2.4 97.9 1.9 334 ARHGEF2 9181 214562 30 101.4 2.5 97.1 3.1 97.4 4 334 ARHGEF2 9181 214562 100 83.5 3.5 93.9 1.8 96.5 2.4 435 PRSS15 9361 105664 10 130.9 14.3 106.4 8.7 106.7 0.6 435 PRSS15 9361 105664 30 96.1 7.7 114.5 2.9 102.9 1.5 435 PRSS15 9361 105664 100 110.9 7.8 112.8 6.1 104 1.4 435 PRSS15 9361 212758 10 140.1 28.8 115.5 3.6 100.4 0.8 435 PRSS15 9361 212758 30 113.8 6.1 115.8 4.9 104.2 2.6 435 PRSS15 9361 212758 100 131.2 14.1 121.6 3.2 107.7 2.1 459 PCYT1B 9468 111523 10 107.8 34.4 116.3 1.7 101.8 1.4 459 PCYT1B 9468 111523 30 113.3 8.7 115.9 1.7 106.4 1.7 459 PCYT1B 9468 111523 100 107.3 11.8 119.2 1.3 106.1 1.4 459 PCYT1B 9468 214260 10 133.6 20.8 108.6 4.5 104 2.6 459 PCYT1B 9468 214260 30 103.6 14.1 109.2 3.6 102.9 1.6 459 PCYT1B 9468 214260 100 101 16.9 109.2 3.4 102.3 2.2 486 FLJ21736 79984 119838 10 129.8 12.4 486 FLJ21736 79984 119838 30 158.8 28.4 486 FLJ21736 79984 119838 100 165.3 25.2 486 FLJ21736 79984 235619 10 129.1 23.3 486 FLJ21736 79984 235619 30 170.4 2.5 486 FLJ21736 79984 235619 100 146.9 23 495 KIR2DS1 3806 212646 10 126.8 7 495 KIR2DS1 3806 212646 30 137.9 16.6 495 KIR2DS1 3806 212646 100 132.8 16.9 495 KIR2DS1 3806 235634 10 117.5 13.2 495 KIR2DS1 3806 235634 30 137.5 30.8 495 KIR2DS1 3806 235634 100 143 5 496 KIR2DS3 3808 213159 10 127.9 8.4 496 KIR2DS3 3808 213159 30 150.6 4 496 KIR2DS3 3808 213159 100 155.8 26.2 496 KIR2DS3 3808 235633 10 122.2 19.5 496 KIR2DS3 3808 235633 30 116.3 13.4 496 KIR2DS3 3808 235633 100 130 12.8 506 MOXD1 26002 111923 10 125.3 6.4 506 MOXD1 26002 111923 30 152.1 20.1 506 MOXD1 26002 111923 100 142 19.8 506 MOXD1 26002 235615 10 134.9 7.5 506 MOXD1 26002 235615 30 145 10.9 506 MOXD1 26002 235615 100 137.7 12.5 514 PEPD 5184 105302 10 84.1 47.7 117.1 4 108.6 1.5 514 PEPD 5184 105302 30 105 1.7 114.9 1.2 104.9 2.4 514 PEPD 5184 105302 100 109 4.3 113 2.8 104.3 2 514 PEPD 5184 212688 10 96.5 43 109.8 6.8 99.9 1.6 514 PEPD 5184 212688 30 102.8 1.1 104.7 3.8 96.9 2.7 514 PEPD 5184 212688 100 121.7 6.4 96.5 4.5 98.5 0.8

TABLE 8 Target % mRNA Target No Symbol Gene Id siRNA ID siRNA conc. Mean 2 HLCS 3141 117852 10 26.6 2 HLCS 3141 117852 30 20.3 2 HLCS 3141 117852 100 13.2 2 HLCS 3141 117853 10 66 2 HLCS 3141 117853 30 54.7 2 HLCS 3141 117853 100 50.6 3 SC4MOL 6307 117417 10 34.4 3 SC4MOL 6307 117417 30 10.8 3 SC4MOL 6307 117417 100 8.3 3 SC4MOL 6307 117418 10 43.5 3 SC4MOL 6307 117418 30 23.4 3 SC4MOL 6307 117418 100 23.4 4 CASP1 834 42626 10 4 CASP1 834 42626 30 4 CASP1 834 42626 100 4 CASP1 834 42711 10 4 CASP1 834 42711 30 4 CASP1 834 42711 100 7 CTSE 1510 105039 10 11.5 7 CTSE 1510 105039 30 26.6 7 CTSE 1510 105039 100 8.2 7 CTSE 1510 105041 10 60.5 7 CTSE 1510 105041 30 62.7 7 CTSE 1510 105041 100 20.8 8 FRK 2444 1147 10 27.7 8 FRK 2444 1147 30 24.4 8 FRK 2444 1147 100 22.4 8 FRK 2444 1243 10 87.2 8 FRK 2444 1243 30 70.6 8 FRK 2444 1243 100 69.2 9 HMBS 3145 8225 10 9 HMBS 3145 8225 30 37.4 9 HMBS 3145 8225 100 31.9 9 HMBS 3145 117844 10 27.3 9 HMBS 3145 117844 30 15.6 9 HMBS 3145 117844 100 12.5 10 HSD17B4 3295 106087 10 10.9 10 HSD17B4 3295 106087 30 9.1 10 HSD17B4 3295 106087 100 11.8 10 HSD17B4 3295 106089 10 39.5 10 HSD17B4 3295 106089 30 23.5 10 HSD17B4 3295 106089 100 13.3 12 OXTR 5021 1766 10 36.9 12 OXTR 5021 1766 30 61.7 12 OXTR 5021 1766 100 9.9 12 OXTR 5021 1947 10 12 OXTR 5021 1947 30 12 OXTR 5021 1947 100 16 TPI1 7167 43820 10 8.7 16 TPI1 7167 43820 30 12.5 16 TPI1 7167 43820 100 21.8 16 TPI1 7167 43916 10 18 16 TPI1 7167 43916 30 28.5 16 TPI1 7167 43916 100 10.7 18 SLC30A2 7780 117693 10 18 SLC30A2 7780 117693 30 18 SLC30A2 7780 117693 100 18 SLC30A2 7780 117695 10 18 SLC30A2 7780 117695 30 18 SLC30A2 7780 117695 100 19 ULK1 8408 118260 10 23.6 19 ULK1 8408 118260 30 130.9 19 ULK1 8408 118260 100 162.7 19 ULK1 8408 118261 10 17.5 19 ULK1 8408 118261 30 24 19 ULK1 8408 118261 100 38.6 22 SPUVE 11098 19104 10 9.7 22 SPUVE 11098 19104 30 28.9 22 SPUVE 11098 19104 100 12 22 SPUVE 11098 19196 10 30 22 SPUVE 11098 19196 30 20 22 SPUVE 11098 19196 100 17.4 27 PKD1L2 114780 104830 10 27 PKD1L2 114780 104830 30 27 PKD1L2 114780 104830 100 27 PKD1L2 114780 104835 10 27 PKD1L2 114780 104835 30 27 PKD1L2 114780 104835 100 39 DNM1L 10059 19471 10 44 39 DNM1L 10059 19471 30 29.9 39 DNM1L 10059 19471 100 10.2 39 DNM1L 10059 214799 10 19.4 39 DNM1L 10059 214799 30 22.4 39 DNM1L 10059 214799 100 21.4 88 GALR2 8811 44971 10 88 GALR2 8811 44971 30 88 GALR2 8811 44971 100 88 GALR2 8811 45063 10 88 GALR2 8811 45063 30 88 GALR2 8811 45063 100 143 SCP2 6342 117110 10 21.5 143 SCP2 6342 117110 30 15.3 143 SCP2 6342 117110 100 4.5 143 SCP2 6342 119182 10 25.7 143 SCP2 6342 119182 30 47.1 143 SCP2 6342 119182 100 16.9 171 PAFAH2 5051 119066 10 26.1 171 PAFAH2 5051 119066 30 18.9 171 PAFAH2 5051 119066 100 15.2 171 PAFAH2 5051 214710 10 14.4 171 PAFAH2 5051 214710 30 9.3 171 PAFAH2 5051 214710 100 11.2 180 GAD2 2572 9108 10 180 GAD2 2572 9108 30 180 GAD2 2572 9108 100 180 GAD2 2572 214716 10 180 GAD2 2572 214716 30 180 GAD2 2572 214716 100 205 HTR2C 3358 1852 10 205 HTR2C 3358 1852 30 205 HTR2C 3358 1852 100 205 HTR2C 3358 1940 10 205 HTR2C 3358 1940 30 205 HTR2C 3358 1940 100 215 LOC345667 345667 104231 10 215 LOC345667 345667 104231 30 215 LOC345667 345667 104231 100 215 LOC345667 345667 212853 10 66.6 215 LOC345667 345667 212853 30 64.8 215 LOC345667 345667 212853 100 56.7 237 GPR3 2827 1785 10 60.4 237 GPR3 2827 1785 30 165.8 237 GPR3 2827 1785 100 82.7 237 GPR3 2827 212766 10 20.2 237 GPR3 2827 212766 30 89.3 237 GPR3 2827 212766 100 85.9 242 DCTD 1635 119612 10 43 242 DCTD 1635 119612 30 37.5 242 DCTD 1635 119612 100 33.9 242 DCTD 1635 214555 10 13.5 242 DCTD 1635 214555 30 11.7 242 DCTD 1635 214555 100 9.6 261 ACLY 47 116939 10 318.9 261 ACLY 47 116939 30 261 ACLY 47 116939 100 13.6 261 ACLY 47 116940 10 38.3 261 ACLY 47 116940 30 30.2 261 ACLY 47 116940 100 33.7 273 AGXT2L1 64850 112236 10 273 AGXT2L1 64850 112236 30 273 AGXT2L1 64850 112236 100 273 AGXT2L1 64850 112237 10 273 AGXT2L1 64850 112237 30 273 AGXT2L1 64850 112237 100 291 ARSE 415 119012 10 17.9 291 ARSE 415 119012 30 18.3 291 ARSE 415 119012 100 11 291 ARSE 415 214706 10 17.7 291 ARSE 415 214706 30 19.3 291 ARSE 415 214706 100 32.9 306 NR2F2 7026 5922 10 61.8 306 NR2F2 7026 5922 30 44.5 306 NR2F2 7026 5922 100 27.2 306 NR2F2 7026 45374 10 74.3 306 NR2F2 7026 45374 30 51.9 306 NR2F2 7026 45374 100 40 309 ADAM18 8749 104120 10 309 ADAM18 8749 104120 30 309 ADAM18 8749 104120 100 309 ADAM18 8749 212787 10 107.7 309 ADAM18 8749 212787 30 94.1 309 ADAM18 8749 212787 100 75 334 ARHGEF2 9181 119230 10 25.8 334 ARHGEF2 9181 119230 30 32.4 334 ARHGEF2 9181 119230 100 40.9 334 ARHGEF2 9181 214562 10 49.7 334 ARHGEF2 9181 214562 30 96.7 334 ARHGEF2 9181 214562 100 21 435 PRSS15 9361 105664 10 24.6 435 PRSS15 9361 105664 30 16.2 435 PRSS15 9361 105664 100 14.8 435 PRSS15 9361 212758 10 1.6 435 PRSS15 9361 212758 30 7.3 435 PRSS15 9361 212758 100 17.9 459 PCYT1B 9468 111523 10 115 459 PCYT1B 9468 111523 30 31.5 459 PCYT1B 9468 111523 100 12.8 459 PCYT1B 9468 214260 10 12.5 459 PCYT1B 9468 214260 30 10.7 459 PCYT1B 9468 214260 100 9.8 486 FLJ21736 79984 119838 10 29.3 486 FLJ21736 79984 119838 30 12.8 486 FLJ21736 79984 119838 100 486 FLJ21736 79984 235619 10 44.1 486 FLJ21736 79984 235619 30 26.7 486 FLJ21736 79984 235619 100 495 KIR2DS1 3806 212646 10 495 KIR2DS1 3806 212646 30 495 KIR2DS1 3806 212646 100 495 KIR2DS1 3806 235634 10 495 KIR2DS1 3806 235634 30 495 KIR2DS1 3806 235634 100 496 KIR2DS3 3808 213159 10 496 KIR2DS3 3808 213159 30 496 KIR2DS3 3808 213159 100 496 KIR2DS3 3808 235633 10 496 KIR2DS3 3808 235633 30 496 KIR2DS3 3808 235633 100 506 MOXD1 26002 111923 10 37.7 506 MOXD1 26002 111923 30 44.7 506 MOXD1 26002 111923 100 506 MOXD1 26002 235615 10 36.9 506 MOXD1 26002 235615 30 46.4 506 MOXD1 26002 235615 100 514 PEPD 5184 105302 10 20.6 514 PEPD 5184 105302 30 6.5 514 PEPD 5184 105302 100 6 514 PEPD 5184 212688 10 55 514 PEPD 5184 212688 30 20.1 514 PEPD 5184 212688 100 32.4

TABLE 9 Target Target siRNA sense sequence SEQ-ID No Symbol Gene Id sirna_id (21-mer) No 2 HLCS   3141 siRNA ID GCCUGAACCUUCUCUUGAGTT 1 2 HLCS   3141 117852 GGACGGUAUGGAGCAUGUUTT 2 2 HLCS   3141 117853 CGAAAGUUAACAAAACUCCTT 3 3 SC4MOL   6307 117416 CCAUUCGUUUAUUAGAAACTT 4 3 SC4MOL   6307 117417 CGUAAACCUUCCUGAAAGATT 5 3 SC4MOL   6307 117418 CCUUUAAUUACCUUCCUAGTT 6 4 CASP1    834  42626 GACUCAUUGAACAUAUGCATT 7 4 CASP1    834  42711 GAAUAUGCCUGUUCCUGUGTT 8 7 CTSE   1510 105039 GGCCCAUAUAUUGCAUUUATT 9 7 CTSE   1510 105040 GGUGUCAUUUGACAUGGUUTT 10 7 CTSE   1510 105041 GGAGGCAGAUAAUGCUGGUTT 11 8 FRK   2444   1147 GGCAGACAAGUCAACCGUGTT 12 8 FRK   2444   1243 GGCAUGGCCACUACUUUGUTT 13 8 FRK   2444   1338 GGACAGUCAAGGUGAUAUATT 14 9 HMBS   3145   8225 GGAAUGCAUGUAUGCUGUGTT 15 9 HMBS   3145 117844 CCAAUCCUACUAAUAAACCTT 16 10 HSD17B4   3295 106087 GGAAUAUAUGGCAACUUUGTT 17 10 HSD17B4   3295 106089 GGGCACACUACACUAUUAATT 18 11 LCN2   3934 121011 CGAGUUACCUCGUCCGAGUTT 19 11 LCN2   3934 121012 GCAUGCUAUGGUGUUCUUCTT 20 12 OXTR   5021   1766 GGUGCACAUCUUCUCUCUGTT 21 12 QXTR   5021   1859 GGCCUACAUCACAUGGAUCTT 22 12 OXTR   5021   1947 GGUACCUAUCAGUUUGUAUTT 23 13 PPP1R3C   5507 142834 CGACGACAUUUUGUGAAUATT 24 13 PPP1R3C   5507 142836 CCGAUUACUUAAGUUUCCGTT 25 16 TPI1   7167  43820 GAGAGAAGGCAUGUCUUUGTT 26 16 TPI1   7167  43916 GAGAAGGCAUGUCUuUGGGTT 27 18 SLC30A2   7780 117693 GCCAGAAUACAAGUAUGUATT 28 18 SLC30A2   7780 117695 CCAUCCUGAGAGAUGUGAUTT 29 19 ULK1   8408 118260 GCGAAUUUUGUGUGAUUUCTT 30 19 ULK1   8408 118261 CCCAAGCACUUUAUGCAUATT 31 22 SPUVE  11098  19104 GGCCAAGCAAUAUCUGUCUTT 32 22 SPUVE  11098  19196 GGGUCUUCAGGAAAGUCUCTT 33 22 SPUVE  11098 212941 CCUAUGUGAAAGGAACCCATT 34 22 SPUVE  11098 212942 CGAGACCUAUGACUUGCUCTT 35 23 PASK  23178    978 GGUCUGAACCAGUGGAUGUTT 36 23 PASK  23178 103354 GGACCAGCAAAUCACUGCCTT 37 26 MYLIP  29116 118397 GGAGCAGACUAGGCAUAUCTT 38 26 MYLIP  29116 118398 GCAGACUAGGCAUAUCUUUTT 39 27 PKD1L2 114780 104830 GGAGGCCAUUUGGUCUUCATT 40 27 PKD1L2 114780 104835 GGCGAUAUGGAGGUGUACATT 41 28 BPHL    670 119221 CGGUUUCAUGCCGACUUCATT 42 28 BPHL    670 214767 GGAAGAGAGCAUGAUAUAUTT 43 29 USP3   9960 105141 GGCAGCCAGACUGCAUUUATT 44 29 USP3   9960 214567 CCAACCAUAAGAAAUCAGATT 45 31 KCNK17  89822 43781 GCUCUAAGGAAGACUUCAATT 46 31 KCNK17  89822 212814 GGAUGCUAUCCAGAGGGACTT 47 31 KCNK17  89822 212815 GGAAGACUUCAAGUCCCAATT 48 32 WEE1   7465    405 GGUAUAUUCAUUCAAUGUCTT 49 32 WEE1   7465 103582 GGACAGUGUCGUCGUAGAATT 50 32 WEE1   7465 103636 GGCUGGAUGGAUGCAUUUATT 51 32 WEE1   7465 212739 CCUGCUAAGAGAAUUACAATT 52 34 RNUT1  10073 117371 CCAUUCUAGAUUGCAUUUATT 53 34 RNUT1  10073 214780 GGGUUCUUCCCAUAGCCCATT 54 35 M6PR   4074 111157 GCGUGGCAAAGUCCAAGAUTT 55 35 M6PR   4074 214744 GGCAUGUGGUUUUGACCUUTT 56 36 MGC39650 147011  38979 GGUGAUCAAGAAGGUAAAGTT 57 36 MGC39650 147011 214871 CGUGAGCCGAUCAUUAAGCTT 58 37 FLJ22761  80201 121933 GGAAUCAUUGCAUGCUUAATT 59 37 FLJ22761  80201 214839 GCCAUCAAGAGGAGAAACGTT 60 38 PAPOLG  64895 119829 GCCUUGAUAUAAGGUGUAUTT 61 38 PAPOLG  64895 214280 CCAUUUGGAGUGUUUGAAGTT 62 39 DNM1L  10059  19471 GGAAAUAAUAAGGGAGUAATT 63 39 DNM1L  10059 214799 GGCUAGCCAGAGAAUUACCTT 64 43 LCN7  64129 105753 GUGGCAGUGUGACCAAGAATT 65 43 LCN7  64129 214577 GCCAGGACACCUCAAGUCUTT 66 45 RASGRP2  10235 120445 GGCUCUGCUAGACCAAGAATT 67 45 RASGRP2  10235 214874 GCAGCCUAAUCGACAUAGATT 68 51 PRPSAP2   5636 117084 GCUCCUGAUCAUGGUGUAUTT 69 51 PRPSAP2   5636 214750 CCAACUUUUUAUGUCGGUUTT 70 52 SLC26A10  65012 119926 GGAGAAAAGGAGACUUCAATT 71 52 SLC26A10  65012 214589 CCUCAUCAUGUGGAGUGGATT 72 56 TNFRSF13B  23495 111813 CCCUAAGCAAUGUGCAUACTT 73 56 TNFRSF13B  23495 214802 GCAAGGCAAGUUCUAUGACTT 74 62 CTSK   1513 105010 GGAAGAGAGUUGUAUGUACTT 75 62 CTSK   1513 214550 GGCUGGAGAUUUUCACAUATT 76 72 D4ST-1 113189 112330 GGAUGUGCUGCCUAAGUAUTT 77 72 D4ST-1 113189 214285 GGCCUUUGAGGUUGUGACUTT 78 73 APCL  10297 121576 CGUGUAAAUAGUGGUAAAUTT 79 73 APCL  10297 214783 CGAACAGUGAUCUACGUCCTT 80 79 ARHGEF1   9138 119422 CCGAUCACAAAGCCUUCUATT 81 79 ARHGEF1   9138 214561 GCCUUCUACGUCCUUUUUATT 82 81 MCCC1  56922 118817 GCCAAAAAACUGGGUGUACTT 83 81 MCCC1  56922 214276 CCAACAUUGACUUCUUACUTT 84 88 GALR2   8811   4818 GGUGACACGCAUGAUCCUCTT 85 89 GALR2   8811  44971 GCACUACCAACCUGUUCAUTT 86 88 GALR2   8811  45063 GCAUCCUGACGGUUGAUGUTT 87 88 GALR2   8811 212858 CCUGUGUUUCAUCCUGUGCTT 88 117 SMPD1   6609   8630 GGUUACAUCGCAUAGUGCCTT 89 117 SMPD1   6609   8725 GGUCUAUUCACCGCCAUCATT 90 117 SMPD1   6609   8816 GGAGACAAAGUGCAUAUAATT 91 117 SMPD1   6609 212695 GCCCAAAUGCUGCUGUGGUTT 92 143 SCP2   6342 117110 CCAGGCAUGUGUUGGCUAUTT 93 143 SCP2   6342 119182 CCUCCUGAUCAAUAAGUAUTT 94 143 SCP2   6342 214903 CGAACUCCUUACUUAUGAATT 95 163 CCM1    889  15563 GGAACGACAGUGGGUAGAUTT 96 163 CCM1    889 214883 GGCUGGUCUCGUGGUAAAATT 97 171 PAFAH2   5051 119066 GCGAGUGUUUACGGGUGUUTT 98 171 PAFAH2   5051 214710 CCCAUGAGCUCCUAUCAAGTT 99 180 GAD2   2572   9108 GGCACAGGUGUAAAUAUAGTT 100 180 GAD2   2572 214716 CGUGCUCUUCUGUUCUCAATT 101 205 HTR2C   3358   1758 GGCCAUCAUGAAGAUUGCUTT 102 205 HTR2C   3358   1852 GGGACGAAGAAAAGGUGUUTT 103 205 HTR2C   3358   1940 GGUGAUGAAUUUACGAUCATT 104 205 HTR2C   3358 144642 GCACUUUCAAUCGUCAUCATT 105 205 HTR2C   3358 212705 GCCCAGUAGCAGCUAUAGUTT 106 215 LOC345667  11174 104231 GGAGGUGGUCUGUAAAAGGTT 107 215 LOC345667  11174 104232 GGCAUCUAGUGACUGUCUATT 108 215 LOC345667  11174 104267 GGGAGACUUGCUUACUGUGTT 109 215 LOC345667  11174 212853 GGUUCAGAAUUCUUAAGUCTT 110 237 GPR3   2827   1785 GGAUGUGCAGAAAGUGCUGTT 111 237 GPR3   2827 212766 CCUCUCUACACCUAUCUUATT 112 240 FLJ32389 126393 122036 CCAAACUGUACAGACUCUCTT 113 240 FLJ32389 128393 214864 CCAGAUAUCCUCGGCAACCTT 114 241 SERPINA7   6906 118553 GCCAAGCAGGAGAUUAACATT 115 241 SERPINA7   6906 214548 GGCCAUUGGCUAAUUGCACTT 116 242 DCTD   1635 119612 CCGAUGUGAAAGGCUGUAGTT 117 242 DCTD   1635 214555 GCAAGAUUGUCAUUGACUUTT 118 261 ACLY     47 116939 GGAGUUCUAUGUCUGCAUCTT 119 261 ACLY     47 116940 GCACGAAGUCACAAUCUUUTT 120 261 ACLY     47 214886 GCAAUUCGAGAUUACCAGGTT 121 273 AGXT2L1  64850 112236 CGACAACAUUGUUGAGUAUTT 122 273 AGXT2L1  64850 112237 GCCAACGAGUUAGGCUUACTT 123 273 AGXT2L1  64850 214281 CCGAAAGUGUGACCUCUGATT 124 291 ARSE    415 119012 GGCUAUGCCACUGGACUCATT 125 291 ARSE    415 214706 CGAGUUCCUGAUGCAUUAUTT 126 292 ITGB8   3696  11202 GGAUUUCAUUUCAGGUGGATT 127 292 ITGB8   3696 214742 CCCUCACAAUUUGUCUCAGTT 128 306 NR2F2   7026   5922 GGCCAUAGUCCUGUUCACCTT 129 306 NR2F2   7026  45374 GAGCUUCUUCAAGCGCAGCTT 130 306 NR2F2   7026 212809 GCUGUUUGUGUUGAAUGCGTT 131 309 ADAM18   8749  21148 GGGAUUUUCGGUUAUUAUATT 132 309 ADAM18   8749 104119 GGGCUCAGUAAAAUGUGGUTT 133 309 ADAM18   8749 104120 GGGAAAGGGAUAUGUAAUATT 134 309 ADAM18   8749 212787 GCAAGAUUUGAGCAUAUAATT 135 334 ARHGEF2   9181 119230 GGUAAUCUACAGUGAGCUGTT 136 334 ARHGEF2   9181 214562 CCAACAUUGCUGGACAUUUTT 137 352 PRP2 134285  43202 GCAUUGGGAUAUUAAGUAGTT 138 352 LOC134285 134285  46549 GUCCUGCUCUCCAUGUUUGTT 139 352 LOC134285 134285 128215 CCGCUAAACGAGACAGACATT 140 352 LOC134285 134285 212841 GGGACAGAUCCAGAUUAUGTT 141 363 PLA2R1  22925 108254 GGUACGCUGUUAAGUAUUATT 142 363 PLA2R1  22925 214723 GCACAUGAGCAGUAAAACATT 143 390 CREB5   9586 116759 GCAAGCGGAAUAUCUCGAUTT 144 390 CREB5   9586 116760 CCUUUUCUGUAUAUAGCCATT 145 390 CREB5   9586 214882 GCAUAAUACCAUCACUACUTT 146 413 FEN1   2237 121476 GCUACUUUGGCCGUAAGGUTT 147 413 FEN1   2237 214763 GCUCUUCUUGGAACCUGAGTT 148 435 PRSS15   9361 105664 GAGAUGACAGCAAUGAGUCTT 149 435 PRSS15   9361 212757 GCAGCUAAAGAUCAUGAAGTT 150 435 PRSS15   9361 212758 GCUAAAGAUCAUCAAGAAGTT 151 441 SYNJ1   8867 104702 GCCAAUCAAGGGUACAUACTT 152 441 SYNJ1   8867 212746 GGCAUUUUAGAACACUUAATT 153 441 SYNJ1   8867 212747 GGCCAUUGAUGUUUUGCUATT 154 459 PCYT1B   9468 111523 CGAAGUUAUCAGAGAUGCUTT 155 459 PCYT1B   9468 214260 CCUCCAGAGAGGGUAUACATT 156 486 FLJ21736  79984 119838 GCAGAUCUUCUCCGUUUCATT 157 486 FLJ21736  79984 235619 CCACUUGACUCUCUGUAAATT 158 489 GPR10   2834 103837 CCGUCUAUGUGUCGGUGUUTT 159 489 GPR10   2834 235614 CCUAUCACGUGGAGCUCAATT 160 495 KIR2DS1   3806 212646 GCAUGGCGUGUGUUGGGUUTT 161 495 KIR2DS1   3806 235634 CCAUCCUCCUCUUCUUUCUTT 162 496 KIR2DS3   3808 213159 GCAUGGCAUGUGUUGGGUUTT 163 496 KIR2DS3   3808 235633 CAGGAAACCCUUCAAAUAGTT 164 498 LOC135896 135896 213242 CCAUUAUGAGCCCAAGAAUTT 165 498 LOC135896 135896 235629 GGCUGCAUCGCUCAAAUCUTT 166 506 MOXD1  26002 111923 GCUGCAUACAUGUGACAUATT 167 506 MOXD1  26002 235615 GCCUUACCAUACUUUGAUCTT 168 507 MPN2 339501 113991 CCAGGGAAUCUCCCUAACUTT 169 507 MPN2 339501 235626 CCCAGUGGUAUGAGGUGAATT 170 514 PEPD   5184 105302 GUACGUAGAUGAGAUUGCCTT 171 514 PEPD   5184 212688 CCAAACAGUGCUGUUUCCCTT 172

TABLE 10 Target Target Gene No Symbol Id RefSeq. Acc. Target description 2 HLCS 3141 NM_000411 Homo sapiens holocarboxylase synthetase (biotin- [proprionyl-Coenzyme A-carboxylase 3 SC4MOL 6307 NM_006745 Homo sapiens sterol-C4-methyl oxidase-like (SC4MOL), mRNA. 4 CASP1 834 NM_033295 Homo sapiens caspase 1, apoptosis-related cysteine protease (interleukin 1, beta, convertase) 7 CTSE 1510 NM_001910 Homo sapiens cathepsin E (CTSE), transcript variant 1, mRNA. 8 FRK 2444 NM_002031 Homo sapiens fyn-related kinase (FRK), mRNA. 9 HMBS 3145 NM_000190 Homo sapiens hydroxymethylbilane synthase(HMBS), mRNA. 10 HSD17B4 3295 NM_000414 Homo sapiens hydroxysteroid (17-beta) dehydrogenase 4 (HSD17B4), mRNA. 11 LCN2 3934 NM_005564 Homo sapiens lipocalin 2 (oncogene 24p3) (LCN2), mRNA. 12 OXTR 5021 NM_000916 Homo sapiens oxytocin receptor (OXTR), mRNA. 13 PPP1R3C 5507 NM_005398 Homo sapiens protein phosphatase 1, regulatory (inhibitor) subunit 3C (PPP1R3C), mRNA. 16 TPI1 7167 NM_000365 Homo sapiens triosephosphate isomerase 1 (TPI1), mRNA. 18 SLC30A2 7780 NM_032513 Homo sapiens solute carrier family 30 (zinc transporter), member 2 (SLC30A2), mRNA. 19 ULK1 8408 NM_003565 Homo sapiens unc-51-like kinase 1 (C. elegans) (ULK1), mRNA. 22 SPUVE 11098 NM_007173 Homo sapiens protease, serine, 23 (PRSS23), mRNA. 23 PASK 23178 NM_015148 Homo sapiens PAS domain containing serine/threonine kinase (PASK), mRNA. 26 MYLIP 29116 NM_013262 Homo sapiens myosin regulatory light chain interacting protein (MYLIP), mRNA. 27 PKD1L2 114780 NM_182740 Homo sapiens polycystic kidney disease 1-like 2 (PKD1L2), transcript variant 2, mRNA. 28 BPHL 670 NM_004332 Homo sapiens biphenyl hydrolase-like (serine hydrolase; breast epithelial mucin-associated antigen) 29 USP3 9960 NM_006537 Homo sapiens ubiquitin specific protease 3 (USP3), mRNA. 31 KCNK17 89822 NM_031460 Homo sapiens potassium channel, subfamily K, member 17 (KCNK17), mRNA. 32 WEE1 7465 NM_003390 Homo sapiens WEE1 homolog (S. pombe) (WEE1), mRNA. 34 RNUT1 10073 NM_005701 Homo sapiens RNA, U transporter 1 (RNUT1), mRNA. 35 M6PR 4074 NM_002355 Homo sapiens mannose-6-phosphate receptor (cation dependent) (M6PR), mRNA. 36 MGC39650 147011 NM_152465 Homo sapiens hypothetical protein MGC39650 (MGC39650), mRNA. 37 FLJ22761 80201 NM_025130 Homo sapiens hypothetical protein FLJ22761 (FLJ22761), mRNA. 38 PAPOLG 64895 NM_022894 Homo sapiens poly(A) polymerase gamma (PAPOLG), mRNA. 39 DNM1L 10059 NM_012062 Homo sapiens dynamin 1-like (DNM1L), transcript variant 1, mRNA. 43 LCN7 64129 NM_022164 Homo sapiens lipocalin 7 (LCN7), mRNA. 45 RASGRP2 10235 NM_153819 Homo sapiens RAS guanyl releasing protein 2 (calcium and DAG-regulated) (RASGRP2), 51 PRPSAP2 5636 NM_002767 Homo sapiens phosphoribosyl pyrophosphate synthetase- associated protein 2 (PRPSAP2), mRNA. 52 SLC26A10 65012 NM_133489 Homo sapiens solute carrier family 26, member 10 (SLC26A10), mRNA. 56 TNFRSF13B 23495 NM_012452 Homo sapiens tumor necrosis factor receptor superfamily, member 13B (TNFRSF13B), mRNA. 62 CTSK 1513 NM_000396 Homo sapiens cathepsin K (pycnodysostosis) (CTSK), mRNA. 72 D4ST1 113189 NM_130468 Homo sapiens dermatan 4 sulfotransferase 1 (D4ST1), mRNA. 73 APCL/APC2 10297 NM_005883 Homo sapiens adenomatosis polyposis coil 2 (APC2), mRNA. 79 ARHGEF1 9138 NM_004706 Homo sapiens Rho guanine nucleotide exchange factor (GEF) 1 (ARHGEF1), transcript variant 2, 81 MCCC1 56922 NM_020166 Homo sapiens methylcrotonoyl-Coenzyme A carboxylase 1 (alpha) (MCCC1), mRNA. 88 GALR2 8811 NM_003857 Homo sapiens galanin receptor 2 (GALR2), mRNA. 117 SMPD1 6609 NM_000543 Homo sapiens sphingomyelin phosphodiesterase 1, acid lysosomal (acid sphingomyelinase) (SMPD1) 143 SCP2 6342 NM_002979 Homo sapiens sterol carrier protein 2 (SCP2), mRNA. 163 CCM1 889 NM_194456 Homo sapiens cerebral cavernous malformations 1 (CCM1), transcript variant 1, mRNA. 171 PAFAH2 5051 NM_000437 Homo sapiens platelet-activating factor acetylhydrolase 2, 40 kDa (PAFAH2), mRNA. 180 GAD2 2572 NM_000818 Homo sapiens glutamate decarboxylase 2 (pancreatic islets and brain, 65 kDa (GAD2), mRNA. 205 HTR2C 3358 NM_000868 Homo sapiens 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C), mRNA. 215 LOC345667 11174 NM_197941 Homo sapiens a-disintegrin-and-metalloprotease with thrombospondin type 1 motif 6 215 LOC345667 345667 NM_197941 Homo sapiens similar to ADAMTS-10 precursor 237 GPR3 2827 NM_005281 Homo sapiens G protein-coupled receptor 3 (GPR3), mRNA. 240 FLJ32389 126393 NM_144617 Homo sapiens heat shock protein, alpha-crystallin-related, B6 (HSPB6), mRNA. 241 SERPINA7 6906 NM_000354 Homo sapiens serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin) 242 DCTD 1635 NM_001921 Homo sapiens dCMP deaminase (DCTD), mRNA. 261 ACLY 47 NM_198830 Homo sapiens ATP citrate lyase (ACLY), transcript variant 2, mRNA. 273 AGXT2L1 64850 NM_031279 Homo sapiens alanine-glyoxylate aminotransferase 2-like 1 (AGXT2L1), mRNA. 291 ARSE 415 NM_000047 Homo sapiens arylsulfatase E (chondrodysplasia punctata 1) (ARSE), mRNA. 292 ITGB8 3696 NM_002214 Homo sapiens integrin, beta 8 (ITGB8), mRNA. 306 NR2F2 7026 NM_021005 Homo sapiens nuclear receptor subfamily 2, group F, member 2 (NR2F2), mRNA. 309 ADAM18 8749 NM_014237 Homo sapiens a disintegrin and metalloproteinase domain 18 (ADAM18), mRNA. 334 ARHGEF2 9181 NM_004723 Homo sapiens rho/rac guanine nucleotide exchange factor (GEF) 2 (ARHGEF2), mRNA. 352 LOC134285 134285 NM_173490 Homo sapiens hypothetical protein LOC134285 (LOC134285), mRNA. 363 PLA2R1 22925 NM_007366 Homo sapiens phospholipase A2 receptor 1, 180 kDa (PLA2R1), mRNA. 390 CREB5 9586 NM_182899 Homo sapiens cAMP responsive element binding protein 5 (CREB5), mRNA. 413 FEN1 2237 NM_004111 Homo sapiens flap structure-specific endonuclease 1 (FEN1), mRNA. 435 PRSS15 9361 NM_004793 Homo sapiens protease, serine, 15 (PRSS15), nuclear gene encoding mitochondrial protein, 441 SYNJ1 8867 NM_003895 Homo sapiens synaptojanin 1 (SYNJ1), transcript variant 1, mRNA. 459 PCYT1B 9468 NM_004845 Homo sapiens phosphate cytidylyltransferase 1, choline, beta isoform (PCYT1B), mRNA. 486 FLJ21736 79984 NM_024922 Homo sapiens esterase 31 489 GPR10 2834 NM_004248 Homo sapiens prolactin releasing hormone receptor 495 KIR2DS1 3806 NM_014512 Homo sapiens killer cell immunoglobulin-like receptor 1 496 KIR2DS3 3806 NM_012313 Homo sapiens killer cell immunoglobulin-like receptor 3 498 LOC135896 135866 NM_001005221 Homo sapiens olfactory receptor, family 4, subfamily F, member 29 506 MOXD1 26002 NM_015529 Homo sapiens monooxygenase, DBH-like 1 507 MPN2 339501 NM_183062 Homo sapiens marapsin 2 514 PEPD 5184 NM_000285 Homo sapiens peptidase D

TABLE 11 LDL-Dil run1 LDL-Dil LDL-Dil run2 LDL-Dil Target No Target Symbol Gene Id siRNA ID Mean % run1 SD % Mean % run2 SD % 2 HLCS 3141 117851 426.6 88.5 2 HLCS 3141 117852 432.1 111.4 2 HLCS 3141 117853 734.4 43.3 3 SC4MOL 6307 117416 366.7 53.0 3 SC4MOL 6307 117417 345.9 27.2 3 SC4MOL 6307 117418 563.4 120.6 4 CASP1 834 42626 285.6 75.4 269.4 118.7 4 CASP1 834 42711 456.2 162.2 250.9 153.6 7 CTSE 1510 105039 546.3 49.5 637.2 42.8 7 CTSE 1510 105040 114.4 16.2 103.1 17.0 7 CTSE 1510 105041 171.8 46.2 152.8 34.6 8 FRK 2444 1147 214.8 6.3 196.7 44.1 8 FRK 2444 1243 289.4 12.2 305.7 9.8 8 FRK 2444 1338 57.4 16.0 57.9 16.7 9 HMBS 3145 8225 461.5 41.1 9 HMBS 3145 117844 240.0 23.8 10 HSD17B4 3295 106087 504.1 31.0 10 HSD17B4 3295 106089 168.1 24.1 225.9 6.6 11 LCN2 3934 121011 408.0 96.1 11 LCN2 3934 121012 281.3 47.5 12 OXTR 5021 1766 223.2 29.7 197.2 22.6 12 OXTR 5021 1859 112.2 11.7 98.2 7.1 12 OXTR 5021 1947 341.8 52.4 313.6 8.2 13 PPP1R3C 5507 142834 259.3 69.1 13 PPP1R3C 5507 142836 291.4 81.0 16 TPI1 7167 43820 268.6 76.3 16 TPI1 7167 43916 613.4 61.9 18 SLC30A2 7780 117693 361.0 48.1 18 SLC30A2 7780 117695 417.5 25.0 19 ULK1 8408 118260 359.7 84.5 19 ULK1 8408 118261 900.1 81.2 22 SPUVE 11098 19104 425.1 14.8 644.6 57.9 22 SPUVE 11098 19196 378.1 11.9 262.9 5.9 22 SPUVE 11098 212941 33.8 5.1 26.1 0.4 22 SPUVE 11098 212942 151.4 37.2 23 PASK 23178 978 220.5 11.7 23 PASK 23178 103354 426.8 55.7 26 MYLIP 29116 118397 600.0 39.7 26 MYLIP 29116 118398 427.7 10.9 27 PKD1L2 114780 104830 196.5 22.2 258.0 30.5 27 PKD1L2 114780 104835 643.6 75.3 28 BPHL 670 119221 1438.1 168.4 28 BPHL 670 214767 212.0 16.0 29 USP3 9960 105141 1754.7 235.5 29 USP3 9960 214567 81.7 14.0 31 KCNK17 89822 43781 668.4 52.8 1237.7 1.7 31 KCNK17 89822 212814 68.8 3.9 31 KCNK17 89822 212815 80.5 12.4 32 WEE1 7465 405 180.2 4.2 188.5 19.0 32 WEE1 7465 103582 206.2 30.3 188.8 29.3 32 WEE1 7465 103636 1082.7 66.5 1574.7 286.1 32 WEE1 7465 212739 94.0 23.4 149.1 7.0 34 RNUT1 10073 117371 1078.8 131.4 34 RNUT1 10073 214780 143.6 20.4 35 M6PR 4074 111157 994.9 56.9 35 M6PR 4074 214744 92.7 10.9 36 MGC39650 147011 38979 1220.6 147.4 36 MGC39650 147011 214871 105.6 20.5 37 FLJ22761 80201 121933 780.4 25.7 37 FLJ22761 80201 214839 90.2 27.1 38 PAPOLG 64895 119829 1316.8 157.7 38 PAPOLG 64895 214280 219.6 18.8 181.0 4.3 39 DNM1L 10059 19471 549.3 58.1 39 DNM1L 10059 214799 409.8 36.5 43 LCN7 64129 105753 1224.3 79.9 43 LCN7 64129 214577 59.6 14.7 45 RASGRP2 10235 120445 945.5 215.1 45 RASGRP2 10235 214874 50.8 9.3 51 PRPSAP2 5636 117084 1329.6 118.7 51 PRPSAP2 5636 214750 127.5 23.4 52 SLC26A10 65012 119926 1670.2 49.7 52 SLC26A10 65012 214589 99.5 21.4 56 TNFRSF13B 23495 111813 882.2 73.0 56 TNFRSF13B 23495 214802 252.6 90.2 62 CTSK 1513 105010 773.5 220.9 62 CTSK 1513 214550 265.0 33.7 72 D4ST-1 113189 112330 606.4 27.7 801.4 72.1 72 D4ST-1 113189 214285 148.0 18.9 149.3 11.5 73 APCL 10297 121576 746.2 76.7 73 APCL 10297 214783 493.9 15.5 79 ARHGEF1 9138 119422 843.4 82.4 79 ARHGEF1 9138 214561 253.0 11.6 81 MCCC1 56922 118817 528.8 15.9 81 MCCC1 56922 214276 39.3 9.6 35.0 8.1 88 GALR2 8811 4818 97.2 16.0 106.1 14.9 88 GALR2 8811 44971 585.7 52.5 638.9 88.2 88 GALR2 8811 45063 77.0 13.7 81.7 29.9 88 GALR2 8811 212858 173.5 15.7 229.8 12.4 117 SMPD1 6609 8630 293.5 17.6 262.1 20.3 117 SMPD1 6609 8725 222.3 51.9 167.8 22.8 117 SMPD1 6609 8816 666.0 192.1 117 SMPD1 6609 212695 243.0 35.6 143 SCP2 6342 119182 676.7 75.9 143 SCP2 6342 214903 47.6 8.7 163 CCM1 889 15563 229.6 30.4 163 CCM1 889 214883 795.9 148.6 171 PAFAH2 5051 119066 385.6 71.3 171 PAFAH2 5051 214710 430.2 77.1 180 GAD2 2572 9108 491.9 145.2 180 GAD2 2572 214716 300.0 43.1 205 HTR2C 3358 1758 166.5 27.1 171.1 9.0 205 HTR2C 3358 1852 404.6 48.1 421.5 52.4 205 HTR2C 3358 1940 58.9 10.9 60.2 0.9 205 HTR2C 3358 144642 75.0 13.5 205 HTR2C 3358 212705 161.2 25.0 215 LOC345667 11174 104231 274.2 19.6 247.1 14.1 215 LOC345667 11174 104232 238.9 30.7 254.0 19.1 215 LOC345667 11174 104267 34.7 7.9 36.3 3.4 215 LOC345667 11174 212853 691.6 168.0 237 GPR3 2827 1785 452.1 51.8 644.0 93.4 237 GPR3 2827 212766 132.2 15.7 240 FLJ32389 126393 122036 410.7 91.6 240 FLJ32389 126393 214864 160.4 21.5 241 SERPINA7 6906 118553 472.2 42.0 241 SERPINA7 6906 214548 879.2 107.2 242 DCTD 1635 119612 685.4 60.3 242 DCTD 1635 214555 304.2 17.8 261 ACLY 47 116939 786.4 89.4 261 ACLY 47 214886 242.0 30.2 273 AGXT2L1 64850 112237 369.4 92.9 273 AGXT2L1 64850 214281 73.4 7.2 91.2 11.6 291 ARSE 415 119012 448.3 100.5 291 ARSE 415 214706 404.4 35.9 292 ITGB8 3696 11202 286.5 35.1 292 ITGB8 3696 214742 299.2 11.2 306 NR2F2 7026 5922 370.5 65.9 483.1 109.7 306 NR2F2 7026 45374 512.2 56.6 575.2 46.1 306 NR2F2 7026 212809 96.9 10.6 309 ADAM18 8749 21148 103.4 9.0 130.6 29.4 309 ADAM18 8749 104119 86.5 27.3 95.0 17.2 309 ADAM18 8749 104120 200.0 10.5 198.5 34.9 309 ADAM18 8749 212787 515.1 8.9 547.4 30.2 334 ARHGEF2 9181 119230 296.2 71.6 334 ARHGEF2 9181 214562 334.6 18.9 352 PRP2 134285 43202 356.9 43.3 352 LOC134285 134285 46549 116.9 5.5 110.9 17.8 352 LOC134285 134285 128215 84.3 4.5 352 LOC134285 134285 212841 59.2 4.2 363 PLA2R1 22925 108254 364.3 36.6 363 PLA2R1 22925 214723 67.2 6.2 390 CREB5 9586 116760 292.1 66.1 390 CREB5 9586 214882 139.2 20.1 413 FEN1 2237 121476 268.3 27.9 413 FEN1 2237 214763 195.5 15.1 435 PRSS15 9361 105664 334.5 21.5 357.9 13.1 435 PRSS15 9361 212757 71.9 6.9 435 PRSS15 9361 212758 308.8 16.0 441 SYNJ1 8867 104702 375.3 12.5 419.8 11.9 441 SYNJ1 8867 212746 41.3 5.5 441 SYNJ1 8867 212747 211.3 45.9 459 PCYT1B 9468 111523 313.2 24.3 459 PCYT1B 9468 214260 309.2 13.2 340.4 30.6 486 FLJ21736 79984 119838 486.4 27.2 486 FLJ21736 79984 235619 308.9 34.1 489 GPR10 2834 103837 573.3 59.1 489 GPR10 2834 235614 222.4 10.1 495 KIR2DS1 3806 212646 830.9 16.5 495 KIR2DS1 3806 235634 312.5 41.6 496 KIR2DS3 3808 213159 884.3 43.1 496 KIR2DS3 3808 235633 337.0 2.7 498 LOC135896 135896 213242 665.1 14.1 498 LOC135896 135896 235629 131.6 9.4 506 MOXD1 26002 111923 378.7 13.1 506 MOXD1 26002 235615 343.3 73.0 507 MPN2 339501 113991 276.2 35.2 507 MPN2 339501 235626 307.6 54.9 514 PEPD 5184 105302 218.9 29.3 273.5 58.1 514 PEPD 5184 212688 301.3 62.5

TABLE 12 Proliferation Proliferation Proliferation Proliferation Target No Target Symbol Gene Id siRNA ID run1 Mean % run1 SD % run2 Mean % run2 SD % 2 HLCS 3141 117851 87.0 2.8 2 HLCS 3141 117852 63.8 15.4 2 HLCS 3141 117853 103.0 6.6 3 SC4MOL 6307 117416 106.8 9.2 3 SC4MOL 6307 117417 78.9 6.3 3 SC4MOL 6307 117418 91.4 13.5 4 CASP1 834 42626 104.4 8.3 4 CASP1 834 42711 102.1 9.8 7 CTSE 1510 105039 125.9 4.7 7 CTSE 1510 105040 125.0 5.0 7 CTSE 1510 105041 117.3 16.3 8 FRK 2444 1147 110.3 4.7 8 FRK 2444 1243 119.8 14.1 8 FRK 2444 1338 127.9 8.4 9 HMBS 3145 8225 99.7 3.5 9 HMBS 3145 117844 109.2 13.3 10 HSD17B4 3295 106087 98.7 6.8 10 HSD17B4 3295 106089 81.6 4.2 82.1 15.4 11 LCN2 3934 121011 93.7 16.8 11 LCN2 3934 121012 113.9 20.4 12 OXTR 5021 1766 103.1 9.1 12 OXTR 5021 1859 103.7 8.2 12 OXTR 5021 1947 114.2 8.3 13 PPP1R3C 5507 142834 108.9 14.8 13 PPP1R3C 5507 142836 104.3 10.4 16 TPI1 7167 43820 102.9 5.1 16 TPI1 7167 43916 97.3 3.2 18 SLC30A2 7780 117693 101.4 2.0 18 SLC30A2 7780 117695 120.1 3.1 19 ULK1 8408 118260 100.8 4.6 19 ULK1 8408 118261 96.1 8.5 20 GLP2R 9340 5053 123.0 5.0 20 GLP2R 9340 5146 121.2 4.8 20 GLP2R 9340 5237 107.7 11.1 22 SPUVE 11098 19104 83.5 12.5 97.4 5.1 22 SPUVE 11098 19196 90.3 14.6 115.2 1.2 22 SPUVE 11098 212941 93.4 4.0 101.1 0.2 22 SPUVE 11098 212942 99.4 10.7 23 PASK 23178 978 104.26 4.35 23 PASK 23178 103354 90.19 2.06 24 OR52A1 23538 2061 113.7 3.1 24 OR52A1 23538 2153 114.2 2.6 24 OR52A1 23538 2240 81.6 7.2 25 RGS17 26575 20024 95.6 7.0 25 RGS17 26575 20115 91.2 6.9 26 MYLIP 29116 118397 91.6 15.2 26 MYLIP 29116 118398 110.6 5.3 27 PKD1L2 114780 104830 91.8 11.1 93.2 7.0 27 PKD1L2 114780 104835 82.5 6.3 28 BPHL 670 119221 92.9 14.3 28 BPHL 670 214767 106.0 6.0 29 USP3 9960 105141 84.0 9.3 29 USP3 9960 214567 106.4 6.1 31 KCNK17 89822 43781 73.0 2.6 94.8 5.1 31 KCNK17 89822 212814 118.0 17.5 31 KCNK17 89822 212815 103.0 2.6 32 WEE1 7465 405 98.4 12.9 32 WEE1 7465 103582 112.7 3.1 32 WEE1 7465 103636 90.5 3.8 32 WEE1 7465 212739 35.7 11.2 52.9 8.8 34 RNUT1 10073 117371 66.7 9.3 34 RNUT1 10073 214780 104.1 4.3 35 M6PR 4074 111157 72.8 2.7 35 M6PR 4074 214744 112.1 26.0 36 MGC39650 147011 38979 77.3 20.6 36 MGC39650 147011 214871 82.4 6.0 37 FLJ22761 80201 121933 92.4 9.2 37 FLJ22761 80201 214839 119.8 3.3 38 PAPOLG 64895 119829 92.2 13.0 38 PAPOLG 64895 214280 102.5 29.7 86.8 14.9 39 DNM1L 10059 19471 88.8 7.1 39 DNM1L 10059 214799 107.3 3.9 42 FKSG79 84636 6196 82.6 14.7 42 FKSG79 84636 214845 105.4 16.3 43 LCN7 64129 105753 83.4 11.2 43 LCN7 64129 214577 98.6 11.2 45 RASGRP2 10235 120445 92.1 3.2 45 RASGRP2 10235 214874 71.2 19.6 51 PRPSAP2 5636 117084 87.8 15.2 51 PRPSAP2 5636 214750 103.8 22.9 52 SLC26A10 65012 119926 87.2 5.9 52 SLC26A10 65012 214589 114.7 5.2 54 OBP2A 29991 121179 80.3 9.5 54 OBP2A 29991 214904 74.8 5.7 56 TNFRSF13B 23495 111813 63.3 6.1 56 TNFRSF13B 23495 214802 92.1 9.8 62 CTSK 1513 105010 87.7 11.9 62 CTSK 1513 214550 89.6 5.2 72 D4ST-1 113189 112330 85.2 5.6 88.2 12.3 72 D4ST-1 113189 214285 117.2 19.8 103.6 8.7 73 APCL 10297 121576 95.3 23.9 73 APCL 10297 214783 64.7 8.2 79 ARHGEF1 9138 119422 103.8 20.4 79 ARHGEF1 9138 214561 98.2 10.1 81 MCCC1 56922 118817 85.7 5.4 81 MCCC1 56922 214276 99.8 16.5 84.0 3.1 88 GALR2 8811 4818 136.1 7.5 88 GALR2 8811 44971 96.8 5.4 88 GALR2 8811 45063 126.0 6.9 88 GALR2 8811 212858 94.0 6.0 84.3 13.0 117 SMPD1 6609 8630 92.9 8.0 117 SMPD1 6609 8725 92.4 5.6 117 SMPD1 6609 8816 94.5 1.7 117 SMPD1 6609 212695 102.2 10.0 143 SCP2 6342 119182 95.7 3.2 143 SCP2 6342 214903 71.3 9.7 163 CCM1 889 15563 81.7 14.4 163 CCM1 889 214883 69.2 31.6 171 PAFAH2 5051 119066 95.3 10.1 171 PAFAH2 5051 214710 105.3 11.1 173 NLGN3 54413 121059 117.4 17.8 173 NLGN3 54413 214826 109.0 6.4 179 VN1R2 317701 43139 91.6 4.2 179 VN1R2 317701 43208 89.8 4.5 179 VN1R2 317701 43274 121.2 16.0 179 VN1R2 317701 212843 91.7 7.3 180 GAD2 2572 9108 88.0 8.3 180 GAD2 2572 214716 84.1 7.3 205 HTR2C 3358 1758 124.4 3.3 205 HTR2C 3358 1852 119.6 12.3 205 HTR2C 3358 1940 117.3 5.6 205 HTR2C 3358 144642 89.8 10.4 205 HTR2C 3358 212705 96.2 3.6 215 LOC345667 11174 104231 117.6 3.2 215 LOC345667 11174 104232 128.2 7.2 215 LOC345667 11174 104267 118.2 9.9 215 LOC345667 11174 212853 80.6 13.6 237 GPR3 2827 1785 71.7 2.4 96.5 17.2 237 GPR3 2827 212766 115.2 5.0 240 FLJ32389 126393 122036 116.0 5.9 240 FLJ32389 126393 214864 116.5 7.5 241 SERPINA7 6906 118553 99.6 19.0 241 SERPINA7 6906 214548 99.4 7.3 242 DCTD 1635 119612 94.2 4.9 242 DCTD 1635 214555 101.1 10.8 261 ACLY 47 116939 82.9 31.2 261 ACLY 47 214886 91.1 20.5 273 AGXT2L1 64850 112237 86.0 0.8 273 AGXT2L1 64850 214281 105.9 1.1 109.2 20.2 291 ARSE 415 119012 103.0 13.4 291 ARSE 415 214706 85.4 10.0 292 ITGB8 3696 11202 116.4 20.3 292 ITGB8 3696 214742 67.6 1.7 306 NR2F2 7026 5922 101.6 8.2 89.4 21.3 306 NR2F2 7026 45374 128.5 7.8 306 NR2F2 7026 212809 104.4 13.4 309 ADAM18 8749 21148 133.6 5.4 309 ADAM18 8749 104119 114.7 5.7 309 ADAM18 8749 104120 103.3 6.7 309 ADAM18 8749 212787 76.6 3.4 82.3 13.2 334 ARHGEF2 9181 119230 87.1 10.5 334 ARHGEF2 9181 214562 107.3 11.4 352 PRP2 134285 43202 94.9 2.7 352 LOC134285 134285 46549 96.8 4.8 352 LOC134285 134285 128215 97.3 23.2 352 LOC134285 134285 212841 85.1 12.9 363 PLA2R1 22925 108254 100.0 15.7 363 PLA2R1 22925 214723 108.5 3.2 390 CREB5 9586 116760 110.1 13.2 390 CREB5 9586 214882 99.4 8.7 413 FEN1 2237 121476 99.5 7.2 413 FEN1 2237 214763 100.8 8.4 435 PRSS15 9361 105664 83.2 4.1 107.9 9.5 435 PRSS15 9361 212757 110.9 12.5 435 PRSS15 9361 212758 94.4 17.8 441 SYNJ1 8867 104702 105.8 1.9 112.4 11.6 441 SYNJ1 8867 212746 91.0 3.2 441 SYNJ1 8867 212747 110.6 15.9 452 SULT4A1 25830 111874 91.9 8.9 452 SULT4A1 25830 214271 111.7 18.6 93.1 12.2 459 PCYT1B 9468 111523 75.4 4.6 459 PCYT1B 9468 214260 117.0 5.0 95.7 9.1 486 FLJ21736 79984 119838 99.7 10.8 486 FLJ21736 79984 235619 113.0 11.4 489 GPR10 2834 103837 108.6 9.9 489 GPR10 2834 235614 98.6 9.6 495 KIR2DS1 3806 212646 62.4 13.1 495 KIR2DS1 3806 235634 104.4 5.1 496 KIR2DS3 3808 213159 93.7 13.2 496 KIR2DS3 3808 235633 99.8 8.6 498 LOC135896 135896 213242 88.5 11.2 498 LOC135896 135896 235629 104.8 14.1 506 MOXD1 26002 111923 95.6 19.1 506 MOXD1 26002 235615 116.1 20.7 507 MPN2 339501 113991 93.3 12.0 507 MPN2 339501 235626 105.9 16.5 514 PEPD 5184 105302 76.9 8.4 99.7 17.6 514 PEPD 5184 212688 108.9 20.3 

1. Method for identifying a compound as being useful in the treatment or prophylaxis of a disease, comprising the steps of (a) providing a first cell expressing a target polypeptide selected from the group listed in Table 10, or a fragment, or a derivative thereof; (b) exposing said first cell to a candidate compound; (c) determining a first level of an activity or property, said activity or property being affected by an activity or property of said target polypeptide; and (d) selecting or discarding said candidate compound, based on a comparison of said first level of said activity or property with a reference level of said activity or property; characterised in that said disease is A disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis.
 2. Use of a method of claim 1 for the screening for substances useful in the treatment or prophylaxis of A disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis.
 3. Method of claim 1 or use of claim 2, wherein said host cell expresses said target polypeptide above wild-type level.
 4. Method or use of any of claims 1 to 3, wherein said target polypeptide expression is recombinant polypeptide expression.
 5. Method or use of any of claims 1 to 4, wherein said compound is selected if said first level of said activity or property is lower than said reference level of said activity or property.
 6. Method or use of any of claims 1 to 4, wherein said compound is selected if said first level of said activity or property is higher than said reference level of said activity or property.
 7. Method or use of any of claims 1 to 6, wherein said reference level is a level obtained from a second cell expressing the target polypeptide at a lower level as compared to said first cell.
 8. Method or use of any of claims 1 to 6, wherein said reference level is the level obtained with said first cell in the absence of the candidate compound.
 9. Method or use of any of claims 1 to 8, wherein said method further comprises contacting the host cell with a known agonist or antagonist of the target polypeptide before determining the first level.
 10. Method or use of any of claims 1 to 9, wherein said activity or property being affected by said activity or property of said target polypeptide is binding affinity of said compound to said target polypeptide.
 11. Use of a method, said method comprising the steps of (a) culturing a population of cells expressing a target polypeptide listed in Table 10, or a functional fragment or derivative thereof; (b) determining a first level of expression and/or activity of said target protein in said population of cells; (c) exposing said population of cells to a compound, or a mixture of compounds; (d) determining a second level of expression and/or activity of said target polypeptide in said population of cells during or after said exposure of said population of cells to the compound, or the mixture of compounds; and (e) comparing said first and said second level; for the screening for substances useful in the treatment or prophylaxis of A disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis.
 12. Method or use of any of claims 1 to 11, wherein said first level of an activity or property is determined with a reporter, said reporter being controlled by a promoter responsive to at least one second messenger.
 13. Method or use of claim 12, wherein said at least one second messenger is cyclic AMP, or Ca2+, or both.
 14. Method or use of claim 12 or 13, wherein said promoter is a cyclic AMP-responsive promoter, an NF-KB responsive promoter, a NF-AT responsive promoter, or a promoter responsive to transcription factors or to nuclear hormone receptors.
 15. Method or use of any of claims 12 to 14, wherein the reporter is luciferase or beta-galactosidase.
 16. Method or use of any of claims 1 to 15, wherein the compound is a low molecular weight compound.
 17. Method or use of any of claims 1 to 15, wherein the compound is a polypeptide.
 18. Method or use of any of claims 1 to 15, wherein the compound is a lipid.
 19. Method or use of any of claims 1 to 15, wherein the compound is a natural compound.
 20. Method or use of any of claims 1 to 15, wherein the compound is an antibody or a nanobody.
 21. Method for identifying a compound as being useful in the treatment or prophylaxis of a disease, comprising the steps of (a) contacting said compound with a target polypeptide selected from the group listed in Table 10, or a fragment, or a derivative thereof; (b) detect binding of said compound to said target polypeptide or detect a change in activity of said target polypeptide; (c) selecting said compound If binding is detected in step (b) or if a change in activity is detected in step (b); characterised in that said disease is A disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis.
 22. Use of a method of claim 21 for screening for compounds, useful in the treatment or prophylaxis of A disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis.
 23. Method or use of any of claims 21 to 22, wherein binding is detected in vitro.
 24. Method or use of any of claims 21 to 23, wherein said target polypeptide is a recombinant polypeptide.
 25. Method or use of any of claims 21 to 24, wherein said compound is selected if the binding affinity is equal to or lower than 10 micromolar.
 26. Method or use of any of claims 21 to 25, wherein said compound is a low molecular weight compound.
 27. Method or use of any of claims 21 to 25, wherein said compound is a polypeptide, or a lipid, or a natural compound, or an antibody or a nanobody.
 28. Use of a compound that inhibits an activity and/or the expression of any of the polypeptides listed in Table 10 in the manufacture of a medicament for the treatment or prophylxis of A disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis.
 29. Use of claim 28, wherein said compound is identified according to any one of the methods or uses of claims 1 to
 27. 30. Use of an agent inhibiting the expression of a polypeptide selected from the group listed in Table 10 for the preparation of a medicament for the treatment or prophylaxis of A disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis.
 31. Use of claim 30, wherein said agent is selected from the group consisting of an antisense RNA encoding said polypeptide; a ribozyme that cleaves the polyribonucleotide encoding said polypeptide; an antisense oligodeoxynucleotide (ODN) enconding said polypeptide; a small interfering RNA (siRNA) that is sufficiently homologous to a portion of the polyribonucleotide such that said siRNA is capable of inhibiting the polyribonucleotide that would otherwise cause the production of said polypeptide; a small interfering RNA (siRNA) having the sequence of any of SEQ ID NO:1 to 172; a microRNA (miRNA) suitable for inhibition of a polypeptide selected from the group listed in Table 10; or a short hairpin RNA (shRNA) suitable for silencing expression of a polypeptide selected from the group listed in Table
 10. 32. Use of claim 31, wherein the nucleotide sequence of said agent is present in a vector.
 33. Use of claim 32, wherein the vector is an adenovirus, a retrovirus, an alphavirus, an adeno-associated virus (AAV), a lentivirus, a herpes simplex virus (HSV) or a sendai virus.
 34. Use of any of claims 31 to 33, wherein said agent is siRNA, and said siRNA comprises a sense strand of 17 to 31 nucleotides which is identical to a region of the coding sequence, or its complementary sequence, of any of the polypeptides of Table
 10. 35. Use of claim 34, wherein the siRNA further comprises a cleavable loop region connecting the sense and the antisense strand.
 36. Vector comprising any of SEQ ID NO:1 to 172
 37. Use of a vector of claim 36 as a medicament.
 38. Use of a vector of claim 37 for the manufacture of a medicament useful in the treatment or prophylaxis of A disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis.
 39. Use according to claim 37 or 38, wherein the vector is an adenoviral, retroviral, adeno-associated viral, lentiviral or a sendaiviral vector.
 40. Method for diagnosing a pathological condition involving A disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis, or a susceptibility to said condition in a subject, comprising (a) obtaining a sample of the subject's mRNA corresponding to a polypeptide selected from the group listed in Table 10, or a sample of the subject's genomic DNA corresponding to a polypeptide of Table 10; (b) determining the nucleic acid sequence of said mRNA or said genomic DNA; (c) obtaining the nucleic acid sequence encoding said polypeptide of Table 10 from a public database; and (d) identifying any difference(s) between the nucleic acid sequences determined in step (b) and (c); wherein a pathological condition involving a disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or a disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis, or a susceptibility to such a condition in a subject is diagnosed, if such difference(s) are identified in step (d).
 41. Method for diagnosing a pathological condition involving A disease selected from the group comprising cardiovascular diseases, disorders of lipid metabolism or atherosclerosis or a susceptibility to such a condition in a subject, comprising (a) determining the amount of a polypeptide of Table 10 in a biological sample of said subject; and (b) comparing the amount determined in (a) with a the amount of the polypeptide in a healthy subject; wherein an increase or a decrease of the amount of said polypeptide compared to the amount present in a healthy subject is indicative of the presence of the pathological condition. 